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Science 312 (5777): 1220-1223

Copyright © 2006 by the American Association for the Advancement of Science

CRACM1 Is a Plasma Membrane Protein Essential for Store-Operated Ca2+ Entry

M. Vig,1* C. Peinelt,2 A. Beck,2 D. L. Koomoa,2 D. Rabah,1 M. Koblan-Huberson,1 S. Kraft,1 H. Turner,2 A. Fleig,2 R. Penner,2* J.-P. Kinet1*

Abstract: Store-operated Ca2+ entry is mediated by Ca2+ release–activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane–resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.

1 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
2 Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI 96813, USA.

* To whom correspondence should be addressed. E-mail: mvig{at} (M.V.); rpenner{at} (R.P.); jkinet{at} (J.-P.K.)

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Mitofusin 2 Regulates STIM1 Migration from the Ca2+ Store to the Plasma Membrane in Cells with Depolarized Mitochondria.
K. Singaravelu, C. Nelson, D. Bakowski, O. M. de Brito, S.-W. Ng, J. Di Capite, T. Powell, L. Scorrano, and A. B. Parekh (2011)
J. Biol. Chem. 286, 12189-12201
   Abstract »    Full Text »    PDF »
Ca2+ Signaling During Mammalian Fertilization: Requirements, Players, and Adaptations.
T. Wakai, V. Vanderheyden, and R. A. Fissore (2011)
Cold Spring Harb Perspect Biol 3, a006767
   Abstract »    Full Text »    PDF »
Competitive Modulation of Ca2+ Release-activated Ca2+ Channel Gating by STIM1 and 2-Aminoethyldiphenyl Borate.
M. Yamashita, A. Somasundaram, and M. Prakriya (2011)
J. Biol. Chem. 286, 9429-9442
   Abstract »    Full Text »    PDF »
Role of the STIM1 C-terminal Domain in STIM1 Clustering.
F. Yu, L. Sun, R. Courjaret, and K. Machaca (2011)
J. Biol. Chem. 286, 8375-8384
   Abstract »    Full Text »    PDF »
ORAI1-Mediated Calcium Influx in Lactation and in Breast Cancer.
D. McAndrew, D. M. Grice, A. A. Peters, F. M. Davis, T. Stewart, M. Rice, C. E. Smart, M. A. Brown, P. A. Kenny, S. J. Roberts-Thomson, et al. (2011)
Mol. Cancer Ther. 10, 448-460
   Abstract »    Full Text »    PDF »
ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis.
A. Maul-Pavicic, S. C. C. Chiang, A. Rensing-Ehl, B. Jessen, C. Fauriat, S. M. Wood, S. Sjoqvist, M. Hufnagel, I. Schulze, T. Bass, et al. (2011)
PNAS 108, 3324-3329
   Abstract »    Full Text »    PDF »
An Essential Role of STIM1, Orai1, and S100A8-A9 Proteins for Ca2+ Signaling and Fc{gamma}R-Mediated Phagosomal Oxidative Activity.
N. Steinckwich, V. Schenten, C. Melchior, S. Brechard, and E. J. Tschirhart (2011)
J. Immunol. 186, 2182-2191
   Abstract »    Full Text »    PDF »
Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry.
L. Zheng, P. B. Stathopulos, R. Schindl, G.-Y. Li, C. Romanin, and M. Ikura (2011)
PNAS 108, 1337-1342
   Abstract »    Full Text »    PDF »
Store-operated Ca2+ signaling in dendritic cells occurs independently of STIM1.
B. C. Bandyopadhyay, S. C. Pingle, and G. P. Ahern (2011)
J. Leukoc. Biol. 89, 57-62
   Abstract »    Full Text »    PDF »
Impaired Orai1-mediated Resting Ca2+ Entry Reduces the Cytosolic [Ca2+] and Sarcoplasmic Reticulum Ca2+ Loading in Quiescent Junctophilin 1 Knock-out Myotubes.
H. Li, X. Ding, J. R. Lopez, H. Takeshima, J. Ma, P. D. Allen, and J. M. Eltit (2010)
J. Biol. Chem. 285, 39171-39179
   Abstract »    Full Text »    PDF »
STIM1-dependent and STIM1-independent Function of Transient Receptor Potential Canonical (TRPC) Channels Tunes Their Store-operated Mode.
K. P. Lee, J. P. Yuan, I. So, P. F. Worley, and S. Muallem (2010)
J. Biol. Chem. 285, 38666-38673
   Abstract »    Full Text »    PDF »
A single lysine in the N-terminal region of store-operated channels is critical for STIM1-mediated gating.
A. Lis, S. Zierler, C. Peinelt, A. Fleig, and R. Penner (2010)
J. Gen. Physiol. 136, 673-686
   Abstract »    Full Text »    PDF »

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