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Dynamin and Myosin Regulate Differential Exocytosis from Mouse Adrenal Chromaffin Cells

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Abstract

Neuroendocrine chromaffin cells of the adrenal medulla represent a primary output for the sympathetic nervous system. Chromaffin cells release catecholamine as well as vaso- and neuro-active peptide transmitters into the circulation through exocytic fusion of large dense-core secretory granules. Under basal sympathetic activity, chromaffin cells selectively release modest levels of catecholamines, helping to set the “rest and digest” status of energy storage. Under stress activation, elevated sympathetic firing leads to increased catecholamine as well as peptide transmitter release to set the “fight or flight” status of energy expenditure. While the mechanism for catecholamine release has been widely investigated, relatively little is known of how peptide transmitter release is regulated to occur selectively under elevated stimulation. Recent studies have shown selective catecholamine release under basal stimulation is accomplished through a transient, restricted exocytic fusion pore between granule and plasma membrane, releasing a soluble fraction of the small, diffusible molecules. Elevated cell firing leads to the active dilation of the fusion pore, leading to the release of both catecholamine and the less diffusible peptide transmitters. Here we propose a molecular mechanism regulating the activity-dependent dilation of the fusion pore. We review the immediate literature and provide new data to formulate a working mechanistic hypothesis whereby calcium-mediated dephosphorylation of dynamin I at Ser-774 leads to the recruitment of the molecular motor myosin II to actively dilate the fusion pore to facilitate release of peptide transmitters. Thus, activity-dependent dephosphorylation of dynamin is hypothesized to represent a key molecular step in the sympatho-adrenal stress response.

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Acknowledgments

We would like to thank Ms. Prattana Samasilp for helpful discussion in the preparation of this manuscript. CS and portions of this work were supported by a Grant from the NIH/NINDS (R01NS052123) and BD was supported by a training Grant from the NIH/NHLBI (T32HL07887).

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  1. Department of Physiology and Biophysics, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, 44106-4970, USA

    Shyue-An Chan, Bryan Doreian & Corey Smith

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  1. Shyue-An Chan
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  2. Bryan Doreian
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Correspondence to Shyue-An Chan.

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A commentary to this article can be found at doi:10.1007/s10571-010-9610-0.

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Chan, SA., Doreian, B. & Smith, C. Dynamin and Myosin Regulate Differential Exocytosis from Mouse Adrenal Chromaffin Cells. Cell Mol Neurobiol 30, 1351–1357 (2010). https://doi.org/10.1007/s10571-010-9591-z

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