SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity

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SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity

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Title: SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity
Author: Carrasquillo, Robert; Tian, Dequan; Krishna, Sneha; Pollak, Martin Russell; Greka, Anna; Schlöndorff, Johannes

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Citation: Carrasquillo, Robert, Dequan Tian, Sneha Krishna, Martin Russell Pollak, Anna Greka, and Johannes Schlöndorff. 2012. SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity. BMC Cell Biology 13:33.
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Abstract: Background: Transient receptor potential canonical (TRPC) channels are non-selective cation channels involved in receptor-mediated calcium signaling in diverse cells and tissues. The canonical transient receptor potential 6 (TRPC6) has been implicated in several pathological processes, including focal segmental glomerulosclerosis (FSGS), cardiac hypertrophy, and pulmonary hypertension. The two large cytoplasmic segments of the cation channel play a critical role in the proper regulation of channel activity, and are involved in several protein-protein interactions. Results: Here we report that SNF8, a component of the endosomal sorting complex for transport-II (ESCRT-II) complex, interacts with TRPC6. The interaction was initially observed in a yeast two-hybrid screen using the amino-terminal cytoplasmic domain of TRPC6 as bait, and confirmed by co-immunoprecipitation from eukaryotic cell extracts. The amino-terminal 107 amino acids are necessary and sufficient for the interaction. Overexpression of SNF8 enhances both wild-type and gain-of-function mutant TRPC6-mediated whole-cell currents in HEK293T cells. Furthermore, activation of NFAT-mediated transcription by gain-of-function mutants is enhanced by overexpression of SNF8, and partially inhibited by RNAi mediated knockdown of SNF8. Although the ESCRT-II complex functions in the endocytosis and lysosomal degradation of transmembrane proteins, SNF8 overexpression does not alter the amount of TRPC6 present on the cell surface. Conclusion: SNF8 is novel binding partner of TRPC6, binding to the amino-terminal cytoplasmic domain of the channel. Modulating SNF8 expression levels alters the TRPC6 channel current and can modulate activation of NFAT-mediated transcription downstream of gain-of-function mutant TRPC6. Taken together, these results identify SNF8 as a novel regulator of TRPC6.
Published Version: doi:10.1186/1471-2121-13-33
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520717/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579566
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