Presented By: LSA Biophysics
Biophysics Seminar: Assistant Prof. Arun Anantharam, University of Michigan
Title: "Optical studies of vesicle dynamics and heterogeneity in exocytosis"
Assistant Professor of Pharmacology
Abstract
The sympathetic nervous system (SNS) is activated by a variety of threats to homeostasis, including injury, hypothermia, psychological distress, and exertion. In response, adrenomedullary chromaffin cells secrete a cocktail of potent catecholamines and neuropeptides, stored within secretory vesicles, into the circulation. The secreted transmitters act in the periphery to drive compensatory or anticipatory changes necessary, in some cases, for survival. By design, the chromaffin cell secretory response is not fixed, but mutable, in order that cellular release properties can be rapidly tuned to physiological requirements. However, the mechanisms underlying the plasticity of this system are unclear. Without this knowledge our understanding of the specificity and subtlety of sympathetic nervous system function will remain limited.
The chromaffin cell secretory response has been modeled extensively using biophysical methods, including measurements of changes in plasma membrane capacitance in stimulated cells. The models are consistent with seemingly interchangeable pools of readily releasable, slowly releasable and reserve vesicles. A major assumption has been that vesicles have the same basic biochemical constituents and that the fusion reaction and the rates of discharge of vesicle contents are uniform. This idea is challenged by our recent findings. Specifically, we discovered that chromaffin vesicles within the same cell can have functionally different isoforms of the key endogenous Ca2+ sensor Synaptotagmin (Syt). These isoforms (Syt-1 and Syt-7) confer different Ca2+ sensitivities to the vesicles in situ enabling them to respond differentially to depolarizing stimuli. Our current hypothesis is that vesicle heterogeneity may provide secretory cells with a rapid and contextually appropriate means of controlling fusion modes and release properties based on local Ca2+ levels. In this seminar, I will present data that supports this hypothesis and discuss implications of functional vesicle heterogeneity for the regulation of the secretory response.
Abstract
The sympathetic nervous system (SNS) is activated by a variety of threats to homeostasis, including injury, hypothermia, psychological distress, and exertion. In response, adrenomedullary chromaffin cells secrete a cocktail of potent catecholamines and neuropeptides, stored within secretory vesicles, into the circulation. The secreted transmitters act in the periphery to drive compensatory or anticipatory changes necessary, in some cases, for survival. By design, the chromaffin cell secretory response is not fixed, but mutable, in order that cellular release properties can be rapidly tuned to physiological requirements. However, the mechanisms underlying the plasticity of this system are unclear. Without this knowledge our understanding of the specificity and subtlety of sympathetic nervous system function will remain limited.
The chromaffin cell secretory response has been modeled extensively using biophysical methods, including measurements of changes in plasma membrane capacitance in stimulated cells. The models are consistent with seemingly interchangeable pools of readily releasable, slowly releasable and reserve vesicles. A major assumption has been that vesicles have the same basic biochemical constituents and that the fusion reaction and the rates of discharge of vesicle contents are uniform. This idea is challenged by our recent findings. Specifically, we discovered that chromaffin vesicles within the same cell can have functionally different isoforms of the key endogenous Ca2+ sensor Synaptotagmin (Syt). These isoforms (Syt-1 and Syt-7) confer different Ca2+ sensitivities to the vesicles in situ enabling them to respond differentially to depolarizing stimuli. Our current hypothesis is that vesicle heterogeneity may provide secretory cells with a rapid and contextually appropriate means of controlling fusion modes and release properties based on local Ca2+ levels. In this seminar, I will present data that supports this hypothesis and discuss implications of functional vesicle heterogeneity for the regulation of the secretory response.
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