How the stimulus defines the dynamics of vesicle pool recruitment, fusion mode, and vesicle recycling in neuroendocrine cells

Abstract

The pattern of stimulation defines important characteristics of the secretory process inneurons and neuroendocrine cells, including the pool of secretory vesicles beingrecruited, the type and amount of transmitters released, the mode of membrane retrievaland the mechanisms associated with vesicle replenishment. This review analyzes themechanisms that regulate these processes in chromaffin cells, as well as in otherneuroendocrine and neuronal models. A common factor in these mechanisms is thespatial and temporal distribution of the Ca2+ signal generated during cell stimulation.For instance, neurosecretory cells and neurons have pools of vesicles with differentlocations with respect to Ca2+ channels, and those pools are therefore differentiallyrecruited following different patterns of stimulation. In this regard, a brief stimulus willinduce the exocytosis of a small pool of vesicles that is highly coupled to voltagedependentCa2+ channels, whereas longer or more intense stimulation will provoke aglobal Ca2+ increase, promoting exocytosis irrespective of vesicle location. The patternof stimulation, and therefore the characteristics of the Ca2+ signal generated by thestimulus, also influences the mode of exocytosis and the type of endocytosis. Indeed,low frequency stimulation favors kiss-and-run exocytosis and clathrin-independent fastendocytosis, whereas higher frequencies promote full fusion and clathrin-dependentendocytosis. This latter type of endocytosis is accelerated at high frequency stimulation.Synaptotagmins, calcineurin, dynamin, complexin, and actin remodeling, appear to beinvolved in the mechanisms that determine the response of these processes to Ca2+.