Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F.

ABSTRACT: TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca²⁺-activated current, we found that the TMEM16F Ca²⁺-response is desensitized by a brief exposure to high intracellular Ca²⁺, which is associated with depletion of phosphatidylinositol-(4, 5)-bisphosphate (PIP₂) from the inner leaflet of the membrane. Application of artificial or natural PIP₂ restores TMEM16F channel activity. PIP₂ modulation of TMEM16F requires the

SUBMITTER: Ye W 

PROVIDER: S-EPMC5816197 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature