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Genome-wide RNAi screen of Ca 2+ influx identifies genes that regulate Ca 2+ release-activated Ca 2+ channel activity

Open access
Zhang, Shenyuan L., Yeromin, Andriy V., Zhang, Xiang H.-F., Yu, Ying, Safrina, Olga, Penna, Aubin, Roos, Jack, Stauderman, Kenneth A., Cahalan, Michael D.·2006·Proceedings of the National Academy of Sciences

Abstract

Recent studies by our group and others demonstrated a required and conserved role of Stim in store-operated Ca 2+ influx and Ca 2+ release-activated Ca 2+ (CRAC) channel activity. By using an unbiased genome-wide RNA interference screen in Drosophila S2 cells, we now identify 75 hits that strongly inhibited Ca 2+ influx upon store emptying by thapsigargin. Among these hits are 11 predicted transmembrane proteins, including Stim , and one, olf186-F , that upon RNA interference-mediated knockdown exhibited a profound reduction of thapsigargin-evoked Ca 2+ entry and CRAC current, and upon overexpression a 3-fold augmentation of CRAC current. CRAC currents were further increased to 8-fold higher than control and developed more rapidly when olf186-F was cotransfected with Stim . olf186-F is a member of a highly conserved family of four-transmembrane spanning proteins with homologs from Caenorhabditis elegans to human. The endoplasmic reticulum (ER) Ca 2+ pump sarco-/ER calcium ATPase (SERCA) and the single transmembrane-soluble N -ethylmaleimide-sensitive (NSF) attachment receptor (SNARE) protein Syntaxin5 also were required for CRAC channel activity, consistent with a signaling pathway in which Stim senses Ca 2+ depletion within the ER, translocates to the plasma membrane, and interacts with olf186-F to trigger CRAC channel activity.

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Metadata

Authors
Zhang, S. L., Yeromin, A. V., Zhang, X. H.-F., Yu, Y., Safrina, O., Penna, A., Roos, J., Stauderman, K. A., & Cahalan, M. D.
Venue
Proceedings of the National Academy of Sciences
Published
2006-06-13
Volume
103
Issue
24
Pages
9357-9362
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2118988881
Cited by
866
References
2
FWCI
27.47
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Genome-wide RNAi screen of Ca 2+ influx identifies genes that regulate Ca 2+ release-activated Ca 2+ channel activity. https://app.cochat.ai/papers/10.1073/pnas.0603161103
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Zhang, S. L., Yeromin, A. V., Zhang, X. H.-F., Yu, Y., Safrina, O., Penna, A., Roos, J., Stauderman, K. A., & Cahalan, M. D. (2006). Genome-wide RNAi screen of Ca 2+ influx identifies genes that regulate Ca 2+ release-activated Ca 2+ channel activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0603161103

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