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Originally published in Science Express on 27 April 2006
Science 26 May 2006:
Vol. 312. no. 5777, pp. 1220 - 1223
DOI: 10.1126/science.1127883
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Reports

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*

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}bidmc.harvard.edu (M.V.); rpenner{at}hawaii.edu (R.P.); jkinet{at}bidmc.harvard.edu (J.-P.K.)

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J. Biol. Chem. 282, 23655-23662
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Murine ORAI2 Splice Variants Form Functional Ca2+ Release-activated Ca2+ (CRAC) Channels.
S. A. Gross, U. Wissenbach, S. E. Philipp, M. Freichel, A. Cavalie, and V. Flockerzi (2007)
J. Biol. Chem. 282, 19375-19384
   Abstract »    Full Text »    PDF »
Calcium Inhibition and Calcium Potentiation of Orai1, Orai2, and Orai3 Calcium Release-activated Calcium Channels.
W. I. DeHaven, J. T. Smyth, R. R. Boyles, and J. W. Putney Jr. (2007)
J. Biol. Chem. 282, 17548-17556
   Abstract »    Full Text »    PDF »
New molecular players in capacitative Ca2+ entry.
J. W. Putney Jr (2007)
J. Cell Sci. 120, 1959-1965
   Abstract »    Full Text »    PDF »
Biochemical and Functional Characterization of Orai Proteins.
Y. Gwack, S. Srikanth, S. Feske, F. Cruz-Guilloty, M. Oh-hora, D. S. Neems, P. G. Hogan, and A. Rao (2007)
J. Biol. Chem. 282, 16232-16243
   Abstract »    Full Text »    PDF »
Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion.
J. Liou, M. Fivaz, T. Inoue, and T. Meyer (2007)
PNAS 104, 9301-9306
   Abstract »    Full Text »    PDF »
Ca2+ mobilization through dorsal root ganglion Ca2+-sensing receptor stably expressed in HEK293 cells.
E. M. Awumey, A. C. Howlett, J. W. Putney Jr., D. I. Diz, and R. D. Bukoski (2007)
Am J Physiol Cell Physiol 292, C1895-C1905
   Abstract »    Full Text »    PDF »
Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases.
S. C. Chung, A. Limnander, T. Kurosaki, A. Weiss, and J. I. Korenbrot (2007)
J. Cell Biol. 177, 317-328
   Abstract »    Full Text »    PDF »
Relocalization of STIM1 for Activation of Store-operated Ca2+ Entry Is Determined by the Depletion of Subplasma Membrane Endoplasmic Reticulum Ca2+ Store.
H. L. Ong, X. Liu, K. Tsaneva-Atanasova, B. B. Singh, B. C. Bandyopadhyay, W. D. Swaim, J. T. Russell, R. S. Hegde, A. Sherman, and I. S. Ambudkar (2007)
J. Biol. Chem. 282, 12176-12185
   Abstract »    Full Text »    PDF »
STIM1 Knockdown Reveals That Store-operated Ca2+ Channels Located Close to Sarco/Endoplasmic Ca2+ ATPases (SERCA) Pumps Silently Refill the Endoplasmic Reticulum.
H. Jousset, M. Frieden, and N. Demaurex (2007)
J. Biol. Chem. 282, 11456-11464
   Abstract »    Full Text »    PDF »
CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility.
C. Lorin-Nebel, J. Xing, X. Yan, and K. Strange (2007)
J. Physiol. 580, 67-85
   Abstract »    Full Text »    PDF »
Dynamic Assembly of TRPC1-STIM1-Orai1 Ternary Complex Is Involved in Store-operated Calcium Influx: EVIDENCE FOR SIMILARITIES IN STORE-OPERATED AND CALCIUM RELEASE-ACTIVATED CALCIUM CHANNEL COMPONENTS.
H. L. Ong, K. T. Cheng, X. Liu, B. C. Bandyopadhyay, B. C. Paria, J. Soboloff, B. Pani, Y. Gwack, S. Srikanth, B. B. Singh, et al. (2007)
J. Biol. Chem. 282, 9105-9116
   Abstract »    Full Text »    PDF »
Role of the store-operated calcium entry proteins Stim1 and Orai1 in muscarinic cholinergic receptor-stimulated calcium oscillations in human embryonic kidney cells.
B. Wedel, R. R. Boyles, J. W. Putney Jr, and G. S. Bird (2007)
J. Physiol. 579, 679-689
   Abstract »    Full Text »    PDF »
Orai proteins interact with TRPC channels and confer responsiveness to store depletion.
Y. Liao, C. Erxleben, E. Yildirim, J. Abramowitz, D. L. Armstrong, and L. Birnbaumer (2007)
PNAS 104, 4682-4687
   Abstract »    Full Text »    PDF »
2006: Signaling Breakthroughs of the Year.
E. M. Adler, N. R. Gough, and L. B. Ray (2007)
Sci. STKE 2007, eg1
   Abstract »    Full Text »    PDF »
Applications of High-Throughput RNA Interference Screens to Problems in Cell and Developmental Biology.
N. Perrimon and B. Mathey-Prevot (2007)
Genetics 175, 7-16
   Abstract »    Full Text »    PDF »
Sustained Activity of Calcium Release-activated Calcium Channels Requires Translocation of Mitochondria to the Plasma Membrane.
A. Quintana, E. C. Schwarz, C. Schwindling, P. Lipp, L. Kaestner, and M. Hoth (2006)
J. Biol. Chem. 281, 40302-40309
   Abstract »    Full Text »    PDF »
Stored Ca2+ Depletion-induced Oligomerization of Stromal Interaction Molecule 1 (STIM1) via the EF-SAM Region: AN INITIATION MECHANISM FOR CAPACITIVE Ca2+ ENTRY.
P. B. Stathopulos, G.-Y. Li, M. J. Plevin, J. B. Ames, and M. Ikura (2006)
J. Biol. Chem. 281, 35855-35862
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A Store-Operated Ca2+ Influx Pathway in the Bag Cell Neurons of Aplysia.
B. A. Kachoei, R. J. Knox, D. Uthuza, S. Levy, L. K. Kaczmarek, and N. S. Magoski (2006)
J Neurophysiol 96, 2688-2698
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Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function.
A. Badou, M. K. Jha, D. Matza, W. Z. Mehal, M. Freichel, V. Flockerzi, and R. A. Flavell (2006)
PNAS 103, 15529-15534
   Abstract »    Full Text »    PDF »
Highlights From The Literature.
(2006)
Physiology 21, 302-306
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Function of a STIM1 Homologue in C. elegans: Evidence that Store-operated Ca2+ Entry Is Not Essential for Oscillatory Ca2+ Signaling and ER Ca2+ Homeostasis.
X. Yan, J. Xing, C. Lorin-Nebel, A. Y. Estevez, K. Nehrke, T. Lamitina, and K. Strange (2006)
J. Gen. Physiol. 128, 443-459
   Abstract »    Full Text »    PDF »


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