Contribution of Coiled-Coil Assembly to Ca²⁺/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes.

ABSTRACT:

Background

TRPC6 is a nonselective cation channel, and mutations of this gene are associated with FSGS. These mutations are associated with TRPC6 current amplitude amplification and/or delay of the channel inactivation (gain-of-function phenotype). However, the mechanism of the gain-of-function in TRPC6 activity has not yet been clearly solved.

Methods

We performed electrophysiologic, biochemical, and biophysical experiments to elucidate the molecular mechanism underlying calmodulin (CaM)-mediated Ca²⁺-dependent inactivation (CDI) of TRPC6. To address the pathophysiologic contribution of CDI, we assessed the actin filament organization in cultured mouse podocytes.

Results

Both lobes of CaM helped induce CDI. Moreover, CaM binding to the TRPC6 CaM-binding do

SUBMITTER: Polat OK 

PROVIDER: S-EPMC6727271 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature