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- W2000642032 abstract "The calcium release-activated calcium (CRAC) channel is activated by depletion of Ca2+ from the ER. Store depletion causes the ER Ca2+ sensor, STIM1, to translocate to sites of close ER-plasma membrane apposition, where it interacts with Orai1, the pore-forming subunit of the CRAC channel and activates Ca2+ entry. STIM1 self-associates in resting cells (Baba et al., PNAS 103:16704, 2006) and further oligomerizes after store depletion (Liou et al., PNAS 104:9301, 2007), an event that triggers the self-assembly and activation of STIM1-Orai1 clusters at ER-PM junctions (Luik et al., Nature 454:538, 2008). STIM1 has several protein interaction domains, including a lumenal sterile alpha motif (SAM) and two putative cytosolic coiled-coil regions. The isolated lumenal EF hand - SAM region is known to oligomerize upon Ca2+ removal in vitro (Stathopulos et al., JBC 281:35855, 2006), but the roles of the coiled-coil domains in the functions of STIM1 in situ are not as well understood. Using fluorescence recovery after photobleaching, co-immunoprecipitation, and blue native PAGE analysis on truncated mutants of STIM1 we show that the two coiled-coil domains of STIM1 affect STIM1 oligomerization in different ways. The ER-proximal coiled-coil is sufficient for the self-association of STIM1 in resting cells but does not by itself support oligomerization in response to store depletion. The distal coiled-coil is required for depletion-induced oligomerization. Mutation of specific residues within the predicted hydrophobic interface of the distal coiled-coil prevents the formation of STIM1 puncta and the activation of CRAC channels. These results reveal an essential role for the distal coiled-coil of STIM1 in the oligomerization step that controls store-operated Ca2+ entry." @default.
- W2000642032 created "2016-06-24" @default.
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- W2000642032 date "2009-02-01" @default.
- W2000642032 modified "2023-09-29" @default.
- W2000642032 title "Essential Roles for Coiled-coil Domains in STIM1 Oligomerization and CRAC Channel Activation" @default.
- W2000642032 doi "https://doi.org/10.1016/j.bpj.2008.12.502" @default.
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