On the structure and mechanism of two-pore channels.

ABSTRACT: In eukaryotes, two-pore channels (TPC1-3) comprise a family of ion channels that regulate the conductance of Na⁺ and Ca²⁺ ions across cellular membranes. TPC1-3 form endolysosomal channels, but TPC3 can also function in the plasma membrane. TPC1/3 are voltage-gated channels, but TPC2 opens in response to binding endolysosome-specific lipid phosphatidylinositol-3,5-diphosphate (PI(3,5)P₂ ). Filoviruses, such as Ebola, exploit TPC-mediated ion release as a means of escape from the endolysosome during infection. Antagonists that block TPC1/2 channel conductance abrogate filoviral infections. TPC1/2 form complexes with the mechanistic target of rapamycin complex 1 (mTORC1) at the endolysosomal surface that couple cellular metabolic state and cytosolic nutrient

SUBMITTER: Kintzer AF 

PROVIDER: S-EPMC5745306 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature