Identification of a single aspartate residue critical for both fast and slow calcium-dependent inactivation of the human TRPML1 channel.

ABSTRACT: Transient receptor potential mucolipin subfamily 1 (TRPML1) is a nonselective cation channel mainly located in late endosomes and lysosomes. Mutations of the gene encoding human TRPML1 can cause severe lysosomal diseases. The activity of TRPML1 is regulated by both Ca²⁺ and H⁺, which are important for its critical physiological functions in membrane trafficking, exocytosis, autophagy, and intracellular signal transduction. However, the molecular mechanism of its dual regulation by Ca²⁺ and H⁺ remains elusive. Here, using a mutant screening method in combination with a whole-cell patch clamp technique, we identified a key TRPML1 residue, Asp-472, responsible for both fast calcium-dependent inactivation (FCDI) and slow calcium-dependent inactivatio

SUBMITTER: Wu G 

PROVIDER: S-EPMC6066319 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature