Phosphatidylinositol 4,5-bisphosphate drives Ca²⁺-independent membrane penetration by the tandem C2 domain proteins synaptotagmin-1 and Doc2β.

ABSTRACT: Exocytosis mediates the release of neurotransmitters and hormones from neurons and neuroendocrine cells. Tandem C2 domain proteins in the synaptotagmin (syt) and double C2 domain (Doc2) families regulate exocytotic membrane fusion via direct interactions with Ca²⁺ and phospholipid bilayers. Syt1 is a fast-acting, low-affinity Ca²⁺ sensor that penetrates membranes upon binding Ca²⁺ to trigger synchronous vesicle fusion. The closely related Doc2β is a slow-acting, high-affinity Ca²⁺ sensor that triggers spontaneous and asynchronous vesicle fusion, but whether it also penetrates membranes is unknown. Both syt1 and Doc2β bind the dynamically regulated plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP₂), but it is unclear whe

SUBMITTER: Bradberry MM 

PROVIDER: S-EPMC6635456 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature