The Role of Complexin in Regulated Exocytosis: a Study Shows That the Snare-binding Protein Complexin is a Positive Regulator of Vesicle Priming in Fast, Calcium-triggered Exocytosis

This work has studied the role of complexin in regulated exocytosis, a key mechanism underlies hormone and neurotransmitter release and understanding of which will help to design therapeutic interventions in a lot of neuronal diseases or endocrine diseases. The work here systematically dissects the vesicle stages leading up to exocytosis using a knockout-rescue strategy in a mammalian model system. The work shows that adrenal chromaffin cells from CPX II knockout mice exhibit a markedly diminished readily releasable vesicle pool, while showing no change in the kinetics of fusion pore dilation or morphological vesicle docking. Overexpression of wildtype CPX II ? but not of SNARE-binding-deficient mutants -- restores the size of the readily releasable pool in knockout cells, and in wildtype cells it markedly enlarges the readily releasable pool. These results suggest that CPXs prime vesicles for exocytosis and, therefore, are positive regulators of Ca2+-triggered exocytosis.