Synaptotagmin I- and II-deficient PC12 cells exhibit calcium-independent, depolarization-induced neurotransmitter release from synaptic-like microvesicles.

Synaptotagmin I- and II-deficient PC12 cells (Shoji-Kasai et al. [1]) were used to compare the role of this protein in the calcium-dependent exocytosis of secretory granules and synaptic-like microvesicles (SLMVs). While neither catecholamine nor protein secretion from secretory granules were altered, the depolarization-induced acetylcholine release from SLMVs was no longer calcium-dependent. We propose that within the exocytotic process of SLMVs, there exist two depolarization-induced steps. One is calcium-dependent and no longer present in synaptotagmin I- and II-deficient cells. The other is induced by depolarization, does not require calcium, and suffices to trigger neurotransmitter release from SLMVs in synaptotagmin I- and II-deficient PC12 cells.