Neurotransmitter release through the exocytotic fusion pore

The exocytotic fusion pore transiently connects the secretory granule and plasma membrane during secretory vesicle fusion. Recent evidence on the properties of the fusion pore measured electrophysiologically suggest that the fusion pore is a lipid structure formed by a tension-driven fusion mechanism. We propose that a macromolecular scaffold of proteins directs and regulates the fusion process by drawing a characteristic plasma membrane dimple into close proximity with the secretory granule. Although the identity of the proteins making up the scaffold are largely unknown, studies on the regulation of exocytosis implicate the GTP binding protein Rab3 and unknown Ca²⁺ binding proteins as part of the scaffold, which appears to behave as a coincidence detector. Simultaneous measurement of fusion and the release of secretory products, along with some unusual properties of secretory granule matrices, have led to the unexpected conclusion that the release of secretory products from the matrix may also be regulated.