Sustained Ca2+ signaling is crucial for lymphocyte activation and effector functions. Store-operated calcium release activated calcium (CRAC) channels play a major role in sustaining calcium signaling in lymphocytes. Previously, we identified the gene encoding CRAC channels as CRACM1 (also known as Orail). CRAC channel deficiency results in severe defects in cytokine secretion in lymphocytes and degranulation in mast cells. Point mutations in CRACMI/Orail have been associated with immune-deficiency in human patients. ST1M1 is a crucial regulator of CRAC channels. However, the precise details of how ST1M1 regulates SOCE through CRAC channels remains unknown. Our genome-wide RNAi screen to identify molecular players involved in SOCE identified SNAP (soluble NSF attachment protein) as an important regulator of SOCE in drosophila S2 cells. RNAi mediated knockdown of alpha-SNAP, the mammalian ortholog of SNAP inhibits SOCE in HEK-293 cells. Here, we propose to understand the regulation of SOCE by alpha-SNAP using the following approach.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR048335-12
Application #
8524179
Study Section
Special Emphasis Panel (ZAR1-MLB (M1))
Project Start
2012-09-01
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
12
Fiscal Year
2012
Total Cost
$61,187
Indirect Cost
$20,927
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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