<b>BIOPHYSICS SEMINAR</b><br>Role of Secretory Granule Heterogeneity in the Regulation of Ca2+-Triggered Exocytosis
Ca2+-triggered exocytosis underlies cell-to-cell communication in a variety of critical contexts, including synaptic transmission and endocrine signaling. For the past several decades, the adrenomedullary chromaffin cell has served as a "Rosetta Stone" for our understanding of this process. Indeed, it was studies in chromaffin cells which established the existence of vesicle/granule pools, fusion modes, and a role for PIP2 in exocytosis. An underlying assumption in previous studies of chromaffin cell secretion was that secretory granules are functionally identical with the same biochemical constituents and the potential for uniform rates of content discharge. This idea is challenged by our recent work. Specifically, we can show that granules harbor functionally different isoforms of the endogenous Ca2+ sensor, Synaptotagmin (Syt). These isoforms confer distinct Ca2+ sensitivities to the vesicles in situ, enabling them to respond differentially to stimuli and to release contents with kinetics that vary by more than an order of magnitude. In this seminar, I will discuss how the molecular and functional heterogeneity of granule populations can influence the overall systems-level properties of neurotransmitter and hormone secretion.