CALCIUM: A Matter of Life or Death http://avaxho.me/blogs/ChrisRedfield New Comprehensive Biochemistry Volume 41 Series Editor G BERNARDI Paris On the cover: The Art Object with the designation ‘‘As with head of Janus’’ (Roman, Republican Period, 207 B.C., Mint: Rome, Bronze, Diameter 1.3 in., Everett Fund, 88.373) is reproduced on the front cover with kind permission of the Museum of Fine Arts, Boston, USA The two designs on the right and left of this Roman coin symbolize Calcium bound by the EF-Hand; these logos were originally designed by Ernesto Carafoli, University of Padova, Italy and adapted by Perry D’Obrenan, University of Alberta, Edmonton, Alberta, Canada Amsterdam � Boston � Heidelberg � London � New York � Oxford Paris � San Diego � San Francisco � Singapore � Sydney � Tokyo Calcium: A Matter of Life or Death Edited by Joachim Krebs NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Go¨ttingen, Germany and Institute of Biochemistry, HPM1, Swiss Federal Institute of Technology, Schafmattstrasse 18, CH-8093 Zu¨rich, Switzerland Marek Michalak Department of Biochemistry, 3-56 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7 Amsterdam � Boston � Heidelberg � London � New York � Oxford Paris � San Diego � San Francisco � Singapore � Sydney � Tokyo Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First edition 2007 Copyright � 2007 Elsevier B.V All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@elsevier.com Alternatively you can submit your request online by visiting the Elsevier web site at http://elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing in Publication Data Calcium: a matter of life or death — (New comprehensive biochemistry; v 41) Calcium – Physiological effect Calcium in the body I Krebs, J (Joachim), 1940– II Michalak, Marek 572.50 16 ISBN: 978-0-444-52805-6 ISBN: 978-0-444-80303-0 (Series) ISSN: 0167-7306 For information on all Elsevier publications visit our website at books.elsevier.com Printed and bounded in Italy 07 08 09 10 11 Contents Preface xvii Other volumes in the series xix List of contributors xxiii History and Evolution of Calcium Biochemistry Chapter The unusual history and unique properties of the calcium signal Ernesto Carafoli 3 Preamble General principles of Ca2+ signaling Calcium is both a first and a second messenger The Ca2+ signal has autoregulatory properties The ambivalent nature of the Ca2+ signal Diseases originating from defects of Ca2+ sensor proteins 6.1 A disease involving gelsolin 6.2 Annexinopathies 6.3 Calpainopathies 6.4 Dysfunctions of neuronal Ca2+ sensor proteins 6.5 Calcium channelopathies 6.5.1 The ryanodine receptor 6.5.2 The plasma membrane voltage-gated Ca2+ channel 6.6 Ca2+ pump defects Some final comments References 10 12 13 14 15 15 16 17 17 18 19 20 20 Chapter The evolution of the biochemistry of calcium Robert J P Williams 23 Introduction Inorganic chemistry of Ca 2.1 Model complex ion chemistry 2.2 Exchange rates Primitive earth conditions Procaryote cellular chemistry: concentrations in the cytoplasm 4.1 The first functions of Ca The initial single cell eucaryotes 5.1 Early mineralization [11] 23 24 25 27 28 28 29 30 33 Contents vii Conclusions References 84 85 Chapter Structural aspects of calcium-binding proteins and their interactions with targets Peter B Stathopulos, James B Ames, and Mitsuhiko Ikura 95 Introduction Calmodulin 2.1 CaM structural topology 2.2 CaM target proteins 2.3 Conformational plasticity for target recognition by CaM 2.4 Transcriptional regulation of CaM Neuronal Ca2+ sensor proteins 3.1 NCS common structural topology 3.2 NCS target proteins 3.3 Target recognition of NCS proteins 3.4 Transcriptional regulation of NCS 3.5 NCS-like proteins S100 protein family 4.1 S100 common structural topology 4.2 S100 target proteins 4.3 Target recognition of S100 proteins 4.4 Transcriptional regulation of S100 proteins The penta-EF-hand family 5.1 Sorcin 5.2 Grancalcin 5.3 Calpain 5.4 Apoptosis-linked gene-2 5.5 Peflin Other 6.1 Eps15 homology domain 6.2 Calcium-binding protein 40 6.3 Nucleobindin (calnuc) 6.4 BM-40 (osteonectin, SPARC) 6.5 Stromal interaction molecule Analogies and disparities References 95 96 97 97 97 99 99 99 99 101 101 101 102 102 103 103 105 105 105 107 107 108 109 109 109 110 111 112 113 114 117 Calcium Homeostasis of Cells and Organelles 125 Chapter Voltage-gated calcium channels, calcium signaling, and channelopathies Erika S Piedras-Renterı´a, Curtis F Barrett, Yu-Qing Cao, and Richard W Tsien 127 viii Contents Basic structural features of voltage-gated Ca2+ channels Brief overview of fundamental functional properties of Ca2+ channels Classifications of Ca2+ channels 3.1 CaV1 (L-type) Ca2+ channels 3.2 CaV2 (N-, P/Q- and R-type) Ca2+ channels 3.3 CaV3 (T-type) Ca2+ channels Structural basis of key functions of Ca2+ channels 4.1 Activation 4.2 Voltage-dependent inactivation 4.3 Ca2+-dependent inactivation 4.4 Ca2+-dependent facilitation 4.5 Selectivity, permeation, and block by divalent cations and protons 4.6 Responsiveness to drugs and toxins Vital biological functions of specific Ca2+ channels in relation to genetic and acquired diseases 5.1 Excitation–contraction coupling exemplified by function of CaV1.1 (a1S) L-type channels 5.1.1 CaV1.1 mutations linked to hypokalemic periodic paralysis 5.1.2 CaV1.1 mutations linked to malignant hyperthermia 5.2 Excitation–transcription coupling and changes in gene expression exemplified by CaV1.2 (a1C) and CaV1.3 (a1D) L-type Ca2+ channels 5.2.1 CaV1.2 mutations linked to Timothy syndrome 5.3 Excitation–secretion coupling: generic properties exemplified by CaV1.4 (a1F) L-type Ca2+ channels 5.3.1 Channelopathies in CaV1.4 L-type Ca2+ channels in retina 5.4 Excitation–secretion coupling at CNS nerve terminals exemplified by function of CaV2.1 P/Q-type Ca2+ channels 5.4.1 Mutations in CaV2.1 (P/Q-type) Ca2+ channels can give rise to migraine 5.4.2 Mutations in CaV2.1 Ca2+ channels may also cause episodic ataxia and epilepsy 5.4.3 Spinocerebellar ataxia type 6: a channelopathy or ‘‘glutaminopathy’’? 5.5 Ca2+ channels in nociception and as targets for pain-alleviating agents, exemplified by CaV2.2 (N-type) Ca2+ channels 5.6 Multifunctional effects of Ca2+ channels exemplified by CaV2.3 (R-type) Ca2+ channels 5.6.1 CaV2.3 (R-type) Ca2+ channels in systemic glucose tolerance 5.6.2 CaV2.3 Ca2+ channels and cardiac arrhythmias 5.6.3 CaV2.3 Ca2+ channels and seizure susceptibility 5.7 Ca2+ entry in support of electrogenesis and Ca2+ regulation exemplified by CaV3 (T-type) Ca2+ channels 5.7.1 CaV3 Ca2+ channels and pain 127 130 131 131 131 132 132 132 133 133 134 137 138 139 139 140 140 141 143 144 145 146 147 148 148 149 150 151 151 151 152 152 Contents ix 5.7.2 CaV3 Ca2+ channels and idiopathic generalized epilepsy 5.7.3 CaV3.2 Ca2+ channels and ASD 5.7.4 CaV3 Ca2+ channels and cancer 5.8 Acquired Ca2+ channelopathies Conclusions References 153 153 153 154 154 155 Chapter Exchangers and Ca2+ signaling Joachim Krebs 167 Introduction The NCX family of NCXs 2.1 Structural aspects 2.2 Alternative splicing and regulation of tissue-specific expression The K+-dependent NCX: NCKX Conclusions References 167 169 169 172 174 176 176 Chapter The plasma membrane calcium pump Claudia Ortega, Saida Ortolano, and Ernesto Carafoli 179 Introduction General aspects Isolation and purification of the calcium pump Cloning of the pump and recognition of isoforms The plasma membrane Ca2+ pumps: structural and regulatory characteristics Isoforms of the PMCA pump Splicing variants Protein interactors of PMCA pumps PMCA pump and disease 9.1 PMCA pump knockout mice 9.2 Hereditary deafness and other disease conditions 10 Conclusions References 179 180 181 182 Chapter Endoplasmic reticulum dynamics and calcium signaling Allison Kraus and Marek Michalak 199 Introduction Ca2+ buffering in the ER lumen 2.1 Ca2+ buffering and ER-resident chaperones 2.1.1 Calreticulin, Grp94, and BiP 2.1.2 PDI-like proteins 2.1.3 Calsequestrin 2.1.4 Reticulocalbins 199 200 200 200 201 202 202 182 185 186 188 189 189 191 194 194 x Contents 2.2 Ca2+ sensing by the ER 2.2.1 Stromal-interacting molecule 2.2.2 SOC ER, a multifunctional signaling organelle 3.1 ER Ca2+ and lipid synthesis 3.2 ER and mitochondria Protein folding and ER chaperones 4.1 Calnexin and calreticulin, ER lectin-like chaperones ER stress and UPR Ca2+ signaling in the ER Impact of ER signaling on disease References 202 203 203 204 204 205 206 207 208 209 210 214 Chapter Structural aspects of ion pumping by Ca2+-ATPase of sarcoplasmic reticulum Chikashi Toyoshima 219 Introduction Architecture of Ca2+-ATPase Transmembrane Ca2+-binding sites Scenario of ion pumping Conclusions References 219 222 222 224 226 228 Chapter 10 Ca2+/Mn2+ pumps of the Golgi apparatus and Hailey–Hailey disease Leonard Dode, Jo Vanoevelen, Ludwig Missiaen, Luc Raeymaekers, and Frank Wuytack 229 Introduction Cellular functions of Ca2+ and Mn2+ in the Golgi apparatus 2.1 Role of Ca2+ and Mn2+ in Golgi-specific enzymatic activities 2.1.1 Glycosyltransferases 2.1.2 Sulfotransferases 2.1.3 Casein kinase, calcium, and milk production 2.1.4 Proteolytic processing 2.2 Role of luminal Ca2+ in trafficking and secretion of proteins Role of the Golgi complex in cellular Ca2+ and/or Mn2+ regulation 3.1 Role of the Golgi Pmr1 in Ca2+ and Mn2+ homeostasis in yeast and implications for resistance to oxidative stress 3.2 Golgi-resident proteins involved in Ca2+ regulation 3.2.1 Ca2+ storage capacity of the Golgi 3.2.2 Ca2+ pumps of the secretory pathway 3.2.3 Ca2+ release channels of secretory pathway membranes 3.3 Does the Golgi contribute to the regulation of cytoplasmic Ca2+ in mammalian cells? 229 230 230 231 232 232 233 233 235 236 236 237 237 240 241 (A) (B) (C) (D) Color Plate 48 Localization of microtubules (MTs), endoplasmic reticulum (ER), IP3 receptors (IP3Rs), and Ca2+ before the first morphological appearance of the second cleavage furrow These representative examples of embryos viewed from (A) a facial and (B–D) animal pole views show the co-localization (see arrowheads) of (A) the MTs, (B) the ER, (C) IP3Rs, and (D) Ca2+ at the site of the future furrows of the second cell division cycle (D) The aequorin-generated image (in pseudo-color) is superimposed on the appropriate bright-field image of the embryo (acquired just prior to the aequorin image) to show the position of the Ca2+ signal more clearly This panel represents 60 s of accumulated luminescence Color scale indicates luminescent flux in photons/pixel Scale bars represent 100 mm The first and second cleavage furrows are labeled in panels (A) and (C) Reproduced with kind permission from Zygote [53] (See Figure 3, p 457) Color Plate 49 The possible cytoskeletal targets of the localized release of Ca2+, as well as other molecular elements reported to be involved in cytokinesis Modified from Figure in [9] The main Ca2+-sensitive target is the calmodulin Ca2+ sensor, which acts via MLCK to organize the actomyosin-based contractile band (See Figure 4, p 463) 544 Color Plate 50 (Continued ) 545 Color Plate 50 (Continued) Possible roles of Ca2+ signaling during cleavage furrow deepening and apposition in zebrafish zygotes Hypothetical model showing a facial view of a zebrafish blastodisc to illustrate how Ca2+ released via the activation of IP3Rs in the ER might generate the furrow deepening transient and how Ca2+ entering from the outside of the embryo through plasma membrane Ca2+ channels might generate the furrow apposition Ca2+ transient The model also suggests that one of the possible downstream functions of these Ca2+ transients is to regulate vesicle recruitment and fusion during ingression and apposition It is suggested that vesicle recruitment might be mediated by cognate v- and t-SNARE partners located on the vesicles and ingressing furrow membrane, respectively It is also proposed that vesicles are transported to the deepening furrow by an array of perpendicular microtubules [55], which may have developed from the pf-MTA (See Figure 5, p 464) Color Plate 51 Summary of the major components of the Ca2+ signalling toolkit Many of the individual components are present in multiple isoforms that further enhance the diversity of the Ca2+ signalling systems The yellow arrows illustrate the ON reactions that introduce Ca2+ into the cell, and the blue arrows depict the OFF reactions that pump Ca2+ either out of the cell or back into the endoplasmic reticulum (ER) During its passage through the cytoplasm, Ca2+ resides temporarily on the Ca2+-binding proteins (CaBPs) that function as buffers, or it can pass through the mitochondria To carry out its signalling function, Ca2+ binds to sensors that then employ a range of effectors to stimulate many different cellular processes InsP3R, inositol 1,4,5-trisphosphate receptor; PLC, phospholipase C; NCX, Na+/Ca2+ exchanger; PMCA, plasma membrane Ca2+-ATPases; ROCs, receptor-operated channels; RYR, ryano­ dine receptor; SOCs, store OCs; SERCA, sarcoplasmic–ER Ca2+-ATPase; SMOCs, second-messenger OCs; VOCs, voltage OCs (See Figure 1, p 486) 546 Color Plate 52 Summary of some of the main modules that are mixed and matched to create different Ca2+ signalling systems (1) Agonists such as the neurotransmitters acetylcholine, glutamate and ATP act directly on receptor-operated channels (ROCs) in the plasma membrane (PM) to allow external Ca2+ to enter the cell (2) Second messengers such as diacylglycerol, cyclic AMP, cyclic GMP and arachidonic acid acting from the cytoplasmic side open second-messenger OCs (SMOCs) in the PM (3) Membrane depolarization (DV) activates voltage OCs (VOCs) in the PM to allow a rapid influx of external Ca2+ (4) Membrane depolarization (DV) activates the CaV1.1 L-type channel that then activates the type ryanodine receptor (RYR1) in skeletal muscle through a direct conformational-coupling mechanism (5) Membrane depolarization (DV) activates VOCs in the PM to allow a rapid influx of external Ca2+ to provide trigger Ca2+that then activates the RYR2 to release Ca2+ stored in the sarcoplasmic reticulum (SR) This mechanism is found in cardiac muscle and neurons (6) Agonists acting on cell-surface receptors generate inositol 1,4,5-trisphosphate (InsP3) that then diffuses into the cell to activate the InsP3 receptor (InsP3R) to release Ca2+ from the endoplasmic reticulum (ER) (See Figure 2, p 488) 547 Color Plate 53 A conformational-coupling hypotheses for store-operated Ca2+ entry as might occur in lymphocytes Entry of Ca2+ depends on activation of a store-operated channel (SOC) such as the Ca2+ release-activated Ca2+ (CRAC) channel When an agonist activates phospholipase C (PLC), the increase in inositol 1,4,5-trisphosphate (InsP3) then releases Ca2+ from the endoplasmic reticulum (ER) and the emptying of the store opens the CRAC channel Store emptying might be detected by the stromal interaction molecule (STIM1), which has an N-terminal EF-hand domain that binds Ca2+ when the store is full As the store empties, Ca2+ comes off STIM causing it to undergo a conformational change that is transmitted through some coupling protein [perhaps an InsP3 receptor (InsP3R) or a ryanodine receptor (RYR)] to open the CRAC channels Formation of this coupling complex appears to depend on cytoskeletal remodelling driven by WAVE2 and controlled through the monomeric G proteins Vav and Rac (See Figure 5, p 492) 548 Color Plate 54 Intracellular waves depend on a process of Ca2+-induced Ca2+ release (CICR) whereby the Ca2+ being released from one channel diffuses across to neighbouring channels that are excited to release further Ca2+ thereby setting up a regenerative wave When such waves meet a cell boundary, they can trigger waves in adjacent cells thus setting up an intercellular wave There is still some debate about the way the wave travels between cells (A) One mechanism proposes that when the intracellular wave reaches the cell boundary, some small molecular weight component, most likely to be Ca2+, diffuses across the gap junction to ignite another intracellular wave in the neighbouring cell (B) An alternative mechanism suggests that the intracellular wave in one cell stimulates the release of ATP through hemichannels, which then diffuses across to ignite a wave in neighbouring cells by acting on P2Y receptors to produce inositol 1,4,5-trisphosphate (InsP3) (See Figure 6, p 494) 549 This page intentionally left blank Index A23187 252, 260, 432, 448, 449, 461, 462 see also Calcium, ionophore Acrosome reaction 427, 428 Actin 14, 62, 64, 65, 72, 96, 103, 107, 189, 427, 431, 448, 462, 493 Action potential 128, 131, 134, 150, 174, 367, 405, 408, 497, 500 Actomyosin 448, 450, 462 Actuator domain 183 A-domain see Actuator domain Adenosinetriphosphatase 12, 32, 65, 169, 180, 181, 184, 194, 199, 219, 221, 222, 224, 226, 230, 237, 242, 250, 252, 254, 279, 305, 319, 345, 368, 373, 427, 475, 490 Adenosinetriphosphate 12, 27, 32, 44, 134, 180, 181, 183, 201, 219, 221, 225, 226, 234, 235, 241–253, 303, 304, 309, 353, 371 Aequorin 144, 237, 240, 241, 432, 434, 447, 448, 449, 458, 459, 467, 474 AIP1 see ALG-2 interacting protein ALG-2 see Apoptosis, apoptosis-linked gene ALG-2 interacting protein 1, 108 Alix see ALG-2 interacting protein �-Repeat 168, 175 Alternative splicing 64, 80, 81, 130, 145, 167, 170, 171–174 2-Aminoethoxydiphenylborate 455 AMP-activated protein kinase 348 AMPK see AMP-activated protein kinase AMPPCP 221, 224 2-APB see 2-Aminoethoxydiphenylborate Analog-to-pulse converter 276 Animal pole 452, 455, 457, 459, 542 Annexin 15, 71, 72, 73, 80, 81, 82, 83, 103, 106 Apoptosis apoptosis-linked gene 78–81, 108 Apposition 205, 451, 452, 453, 459, 463, 465 Arrhythmia arrhythmogenic right ventricular dysplasia 17, 321 ARVD see Arrhythmia, arrhythmogenic right ventricular dysplasia Ataxia 18, 148, 154, 269 ATP see Adenosinetriphosphate ATPase see Adenosinetriphosphatase Autoinhibition 346, 348, 349, 351, 418 Autoinhibitory domain 64, 182, 348, 418 Autophosphorylation 206, 346, 347, 349, 418, 419 Autosomal dominant disorder 255 B-cell anergy 387, 388 Bak 471, 474, 475, 476, 477, 479 BAPTA see 1,2-Bis (2- aminophenoxy)ethano-N, N,N,N -tetraacetic acid tetrakis acetoxymethyl acetoxymethyl ester 433 Bax 471, 474, 475, 476, 477, 478, 479 Bay K 8644 141, 144 Bcl-2 206, 472, 473, 474, 475, 476, 477, 479 Benzothiazepine 319 BiP see Immunoglobulin heavy chain binding protein 1,2-Bis (2-aminophenoxy)ethano-N,N,N, N-tetraacetic acid tetrakis acetoxymethyl 433 ester 387, 433 Blastula 446 BM40 112–113 see also Osteonectin, SPARC Ca2þ influx factor 368, 490 ionophore 252, 260, 387, 416, 432, 448, 449, 451, 461, 462, 472 and integrin binding protein 101 response element 141 Ca2þ release 212, 275, 522 Ca2þ spark frequency 306, 307, 308, 313, 314, 315, 317, 318, 320, 321 Ca2þ transient 9, 12, 53, 60, 74, 185, 244, 255, 271, 272, 305, 306, 307, 309, 313, 315, 319 Cabin 356, 358, 379 CACNA1 see Calcium, channel, calcium channel �˜ subunit gene Cadherin 57, 72 cADPr see Cyclic adenosine-diphosphate ribose Caenorhabditis elegans 96, 174, 206, 236, 239, 290 Calcineurin, 365–390 calcineurin A 102 calcineurin B 102 Calcio-signalsome 268, 277, 282, 486, 487 Calcipressin 379 see also Regulator of Calcineurin; Down syndrome critical region 552 Index Calcium ATPase 179 binding domain 53, 57, 66 blink 499 blip 457 calcium-induced calcium release 437 channel (N-, P/Q- or R-type) Ca2þ channel 18, 102, 131, 132, 138, 146, 147, 148, 149, 404, 407, 409 calcium channel �1subunit gene 18, 63, 128, 154 calcium release activating calcium channel 299, 365 calcium release channel 437 L-type Ca2þ channel 97, 105, 131, 138, 139, 140, 141, 144, 145, 174, 297 T-type Ca2þ channel 18, 132, 149, 152, 153, 154, 417, 427 exchanger 168–176, 181 homeostasis 5, 9, 12, 13, 15, 17, 40, 52, 74, 167, 168, 174, 176, 193, 319 ionophore 252 microdomains 205, 206, 373, 404, 473, 498, 499 oscillation 52, 207, 208, 241, 242, 271, 378, 384, 388, 404, 405, 411–416, 430, 432, 435, 458, 461, 475, 487 puffs 493, 499 pump 180, 181, 183, 186 PMCA see Plasma membrane Ca2þ-transport ATPase SERCA see Sarcoplasmic reticulum, sarco­ (endo) plasmic reticulum Ca2þ-transport ATPase release channel 437 sensor 57, 58–59, 62, 66, 501 sparklets 498 sparks 499 spikes 241, 276, 347, 384, 426, 432, 436 store 59, 300, 306, 307, 325 transient 9, 12, 53, 60, 74, 185, 244, 255, 271, 272, 305, 306, 307, 309, 313, 315, 319 transporter 5, 10, 11, 13, 17, 250, 426 waves 404, 451, 452, 458, 459, 460, 489, 493, 498, 499, 500 Calcium-binding protein 40 110–111 Calcium-dependent facilitation 134 Calcium-dependent inactivation 63, 133–134 Calcium-dependent transcription 174, 368 Calmodulin binding domain 170, 182, 183, 184, 186 dependent adenylyl cyclase 97, 99, 141 dependent kinase 63, 131, 141, 346, 426, 430 CaMK 63, 347 CaMKI 351–353 CaMKII 346 CaMKIII see Eukaryotic elongation factor-2 kinase CaMKIV 353–358 CaMKK 351–358 cascade 347 catalytic domain 102, 183, 346, 374 regulatory domain 65, 102, 183, 186, 346, 348, 379, 380, 381, 382, 383 Calnexin 207–208 Calpain 15–16 Calreticulin 200–201, 207–208 Calsenelin see Downstream regulatory element antagonistic modulator Calsequestrin 202 CaM see Calmodulin cAMP see Cyclic adenosine monophosphate dependent kinase 63, 131, 141, 346, 426, 430 Capacitative Ca2þ entry 59, 367, 368 Carbonic anhydrase-related protein 277 Cardiac muscle 62, 64, 65, 96, 139, 141, 202, 221, 288, 291, 297, 298, 299, 300, 303, 306, 307, 308, 311, 312, 313, 316, 317, 326, 410 Cardiomyocytes 15, 19, 74, 211, 298, 305, 306, 307, 313, 315, 317, 318, 319, 320, 367 Cardiomyopathy 19, 319 CARP see Carbonic anhydrase-related protein Casein kinase 232–233 Caspase 13, 108, 473, 477, 478 Catenin-like domain 171 Cav1 channel 132, 145, 146 see also Calcium, channel, L-type Ca2þ channel Cav2 channel 131, 132, 146 see also Calcium, channel, (N-, P/Q- or R-type) Ca2þ channel Cav3 channel 132 see also Calcium, channel, T-type Ca2þ channel CBD see Calcium, binding domain CBP see CREB, CREB binding protein CBP40 see Calcium-binding protein 40 CCD see Central core disease CDF see Calcium-dependent facilitation CDI see Calcium-dependent inactivation Cell death 473–481 necrotic cell death 472 programmed cell death 13, 85, 485 see also Apoptosis Cell division 66, 80, 81, 271, 446, 447, 449, 450, 451, 452, 455, 457, 458, 459, 462 Index Central core disease 17, 324 Central nervous system 16, 75, 99, 143, 193, 389 Cerebellum 151, 185, 193, 269, 279, 291, 349 Channelopathy 143, 144, 145, 149, 154 Chaperone 33, 200, 201, 202, 204, 206, 207, 208, 209, 210, 477 Chemotaxis 425–427 Chromogranin 281 CIB see Ca2þ, and integrin binding protein CICR see Calcium, calcium-induced calcium release CIF see Ca2þ, influx factor CK1 see Constitutive kinase CLD see Catenin-like domain Cleavage furrow 447, 448, 449, 451, 452, 455, 457, 458, 459, 460, 461, 462 CNS see Central nervous system Confocal microscopy 451, 458, 459, 461 Conotoxin 138, 150 Constitutive kinase 382 Cortex 101, 204, 349, 430, 434, 437, 447, 448, 450, 451, 457 CPVT see Tachycardia, catecholaminergic polymorphic ventricular tachycardia CRAC channel see Calcium, channel, calcium release activating calcium channel CRE binding protein phosphorylation 304–306 CRE see Cyclic adenosine monophosphate and Ca2þ, response element CREB see CRE binding protein CREB binding protein 356, 406 CREB dependent transcription 356, 357, 406, 407, 408, 409 Cryo-EM see Electron microscopy, cryo electron microscopy Crystal structure 55, 60, 65, 71, 79, 81, 107, 108, 172, 221, 224, 226, 231, 248, 273, 346, 375, 386 CSNB see X-linked congenital stationary night blindness CSQ see Calsequestrin Current of CRAC channel 366, 368, 369, 371 Cyclic adenosine-diphosphate ribose 6, 432 Cyclic adenosine monophosphate 141 Cyclophilin 373, 379 Cyclosporin A 373 Cytochrome c 277, 473, 474, 477, 478 Cytokinesis 445, 446, 447, 448, 449, 450, 451, 453, 458, 459, 460, 461, 462, 463, 465 Cytoskeleton 14, 77, 81, 83, 103, 184, 212, 493 553 DAG see Diacylglycerol Danio rerio 452 see also Zebrafish Dantrolene 300, 307, 324 Dendrites 140, 189, 279, 280, 281, 404, 495 Depolarization 127, 128, 129, 131, 132, 139, 141, 144, 145, 151, 173, 297, 299, 308, 309, 312, 314, 318, 323, 357, 407, 408, 437, 496, 499 DHP see 1,4-Dihydropyridine receptor see also Calcium, channel, L-type Ca2þ channel DIABLO 477 Diacylglycerol 367 1,4-Dihydropyridine 131 Dorso-ventral axis 272–273 Down syndrome critical region 379 Downstream regulatory element antagonistic modulator 11, 12, 16, 17, 27, 67 DREAM see Downstream regulatory element antagonistic modulator Drosophila melanogaster 244, 270, 461 DSCR see Down syndrome critical region Dual specificity tyrosinephosphorylation regulated kinase 365 Dumbbell-shaped structure 55, 97, 313 DYRK see Dual specificity tyrosinephosphorylation regulated kinase ECC see Excitation-contraction coupling EF-hand EF-hand principle 53–55 EH-domain see Eps15 homology domain Electron microscopy cryo electron microscopy 311, 314 Endoplasmic reticulum 58, 113, 199–214, 345 Epilepsy 18, 132, 148, 152, 153 Eps15 homology domain 108 ER lumen 114, 199, 200, 203, 204, 205, 206, 208, 209, 210, 212, 277, 369, 474 ER see Endoplasmic reticulum ERp44 201, 277, 278, 278, 281 Eukaryotes 96, 109, 117 Eukaryotic elongation factor-2 kinase 346, 348 Exchange inhibitory peptide 170 Excitation-contraction coupling 139–140, 174, 499, 500 Excitation-transcription coupling 132, 141–143 Exocrine secretion 270 554 Index Familial hemiplegic migraine 147 Fertilization 271–272, 425–439 FHM see Familial hemiplegic migraine FK506 binding protein 293 FK506BP see FK506 binding protein FKBP 310–313 FKBP12, 17, 293, 294, 304, 310, 311, 312, 313, 373, 379 Fluorescence fluorescence resonance energy transfer 276 Forkhead box P3 386 FOXP3 see Forkhead box P3 Frequenin 16, 66, 67, 100, 101 FRET see Fluorescence, fluorescence resonance energy transfer Fura-2 449, 461 GABA see �-Aminobutyric acid �-Aminobutyric acid 144 GCAP see Guanylate cyclase-activating protein Gene expression 52, 62, 85, 141, 153, 199, 358, 386, 388, 389, 403, 406, 411, 413, 415, 416, 475 Germ cells 425 GFP see Green fluorescent protein GFP-IP3R 278 GFP-SYNCRIP 281 see also SYNCRIP Glucose-regulated protein 94 200 Glycogen synthase kinase 273 Glycosyltransferase 231–232 Golgi 229–260 Grancalcin 78, 105, 107 Green fluorescent protein 204, 294, 413, 473 GRP94 see Glucose-regulated protein 94 GSK3 see Glycogen synthase kinase GT see Glycosyltransferase Guanylate cyclase-activating protein 16, 66, 99 Hailey–Hailey disease 221, 230–259 Hairpin loop 295 HDAC4 see Histone deacetylase Heart failure 17, 74, 300, 304, 305, 313, 319–321 Hereditary deafness 191–193 see also Plasma membrane Ca2þ-transport ATPase Hippocalcin 66, 100, 101 Hippocampus 61, 74, 152, 153, 185, 269, 349 Histone deacetylase 356, 358 Hormone 9, 10, 36, 52, 57, 144, 234, 429, 471 Hyperpolarization 426, 432, 458, 497 Hypokalemic periodic paralysis 140 ICRAC see Current of CRAC channel IICR see IP3, IP3-induced calcium release Immune response 77, 379, 384–386, 389, 415 Immunoglobulin heavy chain binding protein 200 Immunophilin 17, 310 Immunosuppression 17, 310, 311, 373, 379 Inositol-1,4,5-trisphosphate receptor 366, 367 Interleukin-2 373 Ion pumping 224–226 Ionomycin 204, 232, 386, 387, 388, 389, 462, 475 IP3 see Inositol-1,4,5-trisphosphate indicator 276–277 IP3-induced calcium release 241, 270, 275, 281 IP3R see IP3 receptor Inositol-trisphosphate receptor 287 IP3R-based IP3 sensor 276–277 IP3R-binding protein released with IP3 275 IP3 receptor 36, 241, 258, 267–282 IQ-motif 63 IRBIT see IP3R, IP3R-binding protein released with IP3 IRIS see IP3R, IP3R-based IP3 sensor Junctin 202, 302, 308, 316–318 Keratinocytes 19, 73, 237, 239, 240, 241, 242, 245, 256–260 Kinesin 280 KN62 347–348 KN93 347, 348, 352 Knock in mice 323 Knock out mice 73, 306, 312, 320 KO mice see Knock out mice Kvchannel interacting protein 66 Kv channel see Voltage-gated potassium channel KvChIP see Kvchannel interacting protein LFS see Low-frequency afferent stimulation Lithium 272, 273 Long-term depression 176, 269, 358 Long-term potentiation 150, 269, 352 Low-frequency afferent stimulation 269 LTD see Long-term depression LTP see Long-term potentiation Lymphocyte energy 325, 367, 371, 415 Lymphocytes 191, 325, 366, 367, 371, 373, 388, 404, 410, 411, 414, 415, 416, 471, 490 1-MA see 1-Methyladenine Malignant hyperthermia 17, 140–141, 307 Manganese 25, 30, 236 MAPK see Mitogen-activated protein kinase Maturation Promoting factor 430 Index MEF2 see Myocyte enhancer factor Membrane oscillators 496 Membrane topology 497 Messenger first 3, 5, 6, RNA 99, 149, 208, 209, 240, 245, 270 second 3–4, 8, 53, 83, 367, 437, 488 1-Methyladenine 429, 431 MH see Malignant hyperthermia Microfilaments 447, 448, 462 Microtubules 66, 279–280, 460, 463 Mitochondrion 5, 12, 17, 203, 205–206, 471–479 Mitogen-activated protein kinase 352, 373 MLCK see Myosin, light chain kinase MmD see Multi-minicore disease MPF see Maturation promoting factor Multi-minicore disease 324 Muscles cardiac 64, 65, 96, 288 fast twitch 59, 60, 417 skeletal 59, 60, 64, 173 slow twitch 60, 380, 417 Myocyte enhancer factor 403, 416–419 Myosin light chain kinase 97, 101, 110, 135, 184, 346, 462, 501 Myotonic dystrophy 290 Myristoyl 66, 99, 101 N-domain see Nucleotide binding domain Naþ/Ca2þ-Exchanger 167–169, 188, 234, 426 see also Sodium calcium exchanger Naþ/Ca2þ(Kþ)-exchanger 174, 234 Naþ/HCO3À cotransporter 276 Naþ/Kþ-ATPase 169, 193, 242 NAADP see Nicotinic acid adenine dinucleotide phosphate NBC see Naþ/HCO3À cotransporter NCKX see Naþ/Ca2þ(Kþ)-exchanger NCS-like protein see Ca2þ, and integrin binding protein NCS see Neuronal calcium sensor target proteins 99–101 NCX see Naþ/Ca2þ-Exchanger NEB see Nuclear envelope breakdown NES see Nuclear export signal Neural plasticity 269, 282 Neuromodulin 134, 184 Neuromuscular disorder 287, 324–325 Neuronal calcium sensor 66–67, 501 NFAT see Nuclear factor of activated T-cells NF�B 379, 384, 387, 413, 415–416, 419 Nicotinic acid adenine dinucleotide phosphate 425 555 Nifedipine 131, 428, 453 Nimodipine 131, 407 Nitric oxide synthase 97, 406 Nitrogen oxide 8, 44, 99, 188, 436 NLS see Nuclear localization signal NMDA receptor 367, 407–408, 409, 410 NMR see Nuclear magnetic resonance NO see Nitrogen oxide NOS see Nitric oxide synthase Nuclear envelope breakdown 271, 477 Nuclear export signal 383 Nuclear factor of activated T-cells 188, 210, 273 Nuclear localization signal 149, 349, 381 Nuclear magnetic resonance 57, 170, 271 Nucleobindin 111–112, 117, 235 Nucleotide binding domain 222, 224, 225, 227, 248, 254 Nucleus 32, 62, 74, 80, 105, 142, 149, 153, 240, 259, 348–349, 353, 354, 407, 409–410, 413, 418 Oocytes 79, 204, 207, 272, 368, 429–433, 435 Orai 371–373, 389, 491 see also Calcium, channel, calcium release activating calcium channel; Store-operated calcium entry; Stromal interaction molecule Osteonectin 56, 112 P-domain see Phosphorylation, domain P-type pump 179, 180–181, 182 see also Plasma membrane Ca2þ-transport ATPase; Sarcoplasmic reticulum, Sarco­ (endo) plasmic reticulum Ca2þ-transport ATPase; Secretory pathway Ca2þ-transport ATPase; Naþ/Kþ-ATPase P400 see IP3 receptor PDI see Protein disulphide isomerase PDZ-domain 83, 184, 188 Peflin 78, 80, 105, 109 Phosphatidylinositol-4,5-bisphosphate 367 Phospho-CREB 358 see also CREB Phospholamban 19, 74, 221, 305–306, 319, 320 Phospholipase 12, 15, 56, 81, 472 Phospholipase C 9, 58, 83, 172, 427 Phospholipid binding domain 82, 184 see also Plasma membrane Ca2þ-transport ATPase Phosphoryl transfer 225–226 Phosphorylation domain 184, 224, 304–306 Photoreceptor 16, 17, 66–67, 133, 145, 174, 207 PIP2 see Phosphatidylinositol-4,5-bisphosphate 556 Index PKA see Protein kinase A PKC see Protein kinase C Plasma membrane Ca2þ-transport ATPase 179–194 Plasticity 74, 83, 97–99, 112, 113, 117, 269, 406, 409, 485 PLC see Phospholipase C PMCA see Plasma membrane Ca2þ-transport ATPase Point mutation 57, 191, 203, 321, 324, 348 PP2A see Protein phosphatase Presenilin 16, 67, 100, 213 Procaryotes 34, 36, 39 Proliferation 79, 113, 258, 373, 490 14-3-3 protein 188, 350, 358 Protein disulphide isomerase 200 Protein folding 199–200, 206 Protein kinase A 173, 189, 349, 358, 405 Protein Kinase C 73, 184, 269, 367 Protein phosphatase 10, 102, 281 Proteins ALG-2 78, 79, 108 C2-domain 83–84 calcium-binding 51–85 calcium-buffer 59–61 calcium sensor 7, 13–14, 16–17, 60, 62–64, 83, 95–96, 99, 114, 117, 501 CaM-binding 55, 63–64, 410 EF-hand 7, 11, 14, 16, 53–65, 59, 61, 62, 66, 67, 81–82, 85, 105, 107–108, 109 non-EF-hand 14, 84 PEF 54, 78 penta EF-hand 78–81, 105, 108, 111, 117 S100 67, 69, 70, 71 Pseudo EF-hand 60, 70, 102–103 see also EF-hand Pulse generator 276 see also Analog-to-pulse converter Purkinje cells 185, 268, 279, 291, 358, 495 RAGE see Receptor for advanced glycation end products Rapamycin 310–313 RBM22 80–81 RCAN see Regulator of Calcineurin Recoverin 16–17, 66–67, 99, 101 Receptor for advanced glycation end products 67 Redox sensor 277–278 status 303–304 Regulator of Calcineurin 7, 102, 188, 406, 414 Reticulocalbin 202, 237 Retina 17, 99–100, 145–146, 174, 370 RNA interference 241, 360, 369 RNAi see RNA interference Ruthenium red 292, 300, 437 Ryanodine receptor 74, 97, 105–106, 131, 199, 241, 287–326 Ryanodine 287–327 RyR see Ryanodine receptor accessory proteins 308–318 foot structure 295 pathophysiology 287–326 Sarcoplasmic reticulum Sarco-(endo) plasmic reticulum Ca2þ-transport ATPase 179, 229, 427 SCID see Severe combined immune deficiency Sea urchin 271, 290, 426, 428, 429, 432, 435, 436, 447, 448, 449, 461, 463 Secreted protein acidic and rich cysteine 112 Secretory pathway Ca2þ-transport ATPase 179, 229, 242 Seizure 151–152, 269 SERCA see Sarcoplasmic reticulum, Sarco-(endo) plasmic reticulum Ca2þ-transport ATPase Severe combined immune deficiency 203 SH2 domain see Src homology-2 domain Signaling center 268, 277, 281–282 Signalsome 486, 487 Single channel recording 278, 291, 296, 300, 301, 302, 303, 305, 307, 308, 309, 312, 314, 315, 317, 318, 322–323, 325 Skeletal muscle 17, 19, 60, 107, 139–140, 173, 290–291, 313, 318, 324, 389, 490 SNAP25 see Synaptosome-associated protein 25 SNARE see Soluble NSF-attachment protein receptor SOC see Store-operated Ca2þ-channel SOCE see Store-operated calcium entry Sodium calcium exchanger 167–174, 181 Soluble NSF-attachment protein receptor 369 Sorcin 105–106, 315–316 SPARC see Secreted protein acidic and rich cysteine Spatio-temporal dynamics 372 SPCA see Secretory pathway Ca2þ-transport ATPase Spermatozoa 240, 242, 425, 427, 435, 497 Splicing alternative splicing 64, 81, 172–174, 186, 290 isoforms 67, 186, 187 Src homology-2 domain 435 Starfish oocytes 272, 436, 437, 438 STIM see Stromal interaction molecule Store-operated Ca2þ-channel 114, 203–204, 367, 490–3 Store-operated calcium entry 113–114, 367, 368– 369, 371, 372 Index Stromal interaction molecule 58–59, 113–114, 369, 370 Sulfotransferase 231, 232 Synaptosome-associated protein 25 369 Synaptotagmin Synaptotagmin-binding cytoplasmic RNA-interacting protein 280–281 SYNCRIP see Synaptotagmin, Synaptotagmin-binding cytoplasmic RNA-interacting protein T-cell activation 385–386, 388, 411 anergy 387–388 receptor 80, 367, 387, 411, 413 response 358 T-tubules 139, 297, 299–300, 315 Tachycardia catecholaminergic polymorphic ventricular tachycardia 17, 307, 323–324 Target recognition 95, 96, 97–99, 101, 103–104, 114, 117 TGES motif 222 Thapsigargin 204, 206, 213, 221, 235, 368, 427, 475, 477 Thioredoxin 201, 277, 316 Three-dimensional structure 77, 273–275, 293, 319, 326, 473 Timothy syndrome 143–144 Topology 84, 97, 99, 102–103, 114, 170, 294–296, 372 Transcription factor 16, 75, 112, 142, 149, 193, 199, 205, 208, 209, 210, 245, 356, 358, 366, 373, 375, 380, 384, 385, 386, 388, 389, 405–406, 410–411, 413, 415–416, 418–419 557 Transient receptor potential ion channel 5, 72, 257, 367, 427 Triadin 202, 302, 304, 308, 316–318 TRP ion channel see Transient receptor potential ion channel Unfolded protein response 204, 208–209, 211, 521 UPR see Unfolded protein response VDI see Voltage-dependent inactivation Vegetal pole 459 Vertebrates 41, 51, 62, 64, 78, 100, 168, 236, 237, 244, 245, 288, 290, 297, 311, 380, 416 Vesicular ER 279–280 VGCC see Voltage-gated calcium channel VILIP see Visinin-like protein Visinin-like protein 16, 66, 100 Visinin 16, 66, 100 VOC see Voltage-operated channel Voltage-dependent inactivation 133 Voltage-gated calcium channel 127–155 Voltage-gated potassium channel 127–130 Voltage-operated channel 487, 488, 489, 490, 497 X-linked congenital stationary night blindness 145–146 X-ray crystallography 57, 62, 96, 170, 223, 246, 310, 316, 374, 376, 379 Xenopus laevis 173, 272, 447, 456, 543 XIP see Exchange inhibitory peptide Yeast 66–67, 72, 80, 189, 230, 235, 236, 244, 249, 250 Yeast two hybrid assay 72, 80, 310, 311 Zebrafish 80, 450, 452–455, 457, 459, 463, 465, 546 This page intentionally left blank ... Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing in Publication Data Calcium: a matter of life or death — (New. .. ER-GenTech laboratory and Interdisciplinary Centre for the Study of Inflammation (ICSI), University of Ferrara, Via Borsari 46, 4410 0 Ferrara, Italy Luigia Santella 425 Cell Signaling Laboratory, Stazione... signaling The advancement of knowledge rapidly became all-encompassing: as large amounts of new information were gathered, it gradually became clear that Ca2+ had a number of proper­ ties that made