Diacylglycerols interact with the L2 lipidation site in TRPC3 to induce a sensitized channel state.

ABSTRACT: Coordination of lipids within transient receptor potential canonical channels (TRPCs) is essential for their Ca²⁺ signaling function. Single particle cryo-EM studies identified two lipid interaction sites, designated L1 and L2, which are proposed to accommodate diacylglycerols (DAGs). To explore the role of L1 and L2 in TRPC3 function, we combined structure-guided mutagenesis and electrophysiological recording with molecular dynamics (MD) simulations. MD simulations indicate rapid DAG accumulation within both L1 and L2 upon its availability within the plasma membrane. Electrophysiological experiments using a photoswitchable DAG-probe reveal potentiation of TRPC3 currents during repetitive activation by DAG. Importantly, initial DAG exposure generates a subsequently sensitized ch

SUBMITTER: Erkan-Candag H 

PROVIDER: S-EPMC9253791 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature