Modeling F-actin cortex influence on the secretory properties of neuroendocrine cells

Abstract

Chromaffin cells are considered as one of the most valuable models to study regulated exocytosis. In these cells, like in other neuroendocrine systems, an intricate cortical cytoskeleton acts as a retentive network impeding vesicle access to plasma membrane. Therefore during stimulation this structure suffers a transient reorganization allowing active transport of vesicles toward secretory sites. Interestingly, a combination of confocal microscopy studies and mathematical modeling is showing us new aspects of the influence of cortical cytoskeleton in shaping the secretory properties of excitable cells. In this new vision the F-actin-myosin II cortical cytoskeleton is organized forming polygonal cages with the molecular machinery of exocytosis composed by SNARE proteins and voltage-dependent calcium channels associating with its border. In this way the cytoskeleton not only hold together the essential elements acting during secretion but we proposed that could also act as a structural factor opposing to the free diffusion of the calcium signal and therefore sustains high levels of the intracellular signal triggering exocytosis. 

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Acknowledgments

This work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN, BFU200800731) and the Generalitat Valenciana (ACOMP2009/044) to L.M.G., and Fundación BBVA and I-MATH project C3-0136 to A.G.

Figures and Tables

Figure 1 (A) 3-D reconstruction of the F-actin cortex of a cultured chromaffin cell based in transmitted light images from different planes. The image shows the characteristic network and cages formed by the F-actin cortex. (B) Heterogeneity of intracellular calcium signals during chromaffin cell stimulation. Simultaneous observation of the maximum levels of Fluo-3 signals ([Ca²⁺]_i in green) and transmitted light images of F-actin cytoskeleton (red) showing the spatial coincidence of Fluo-3 signals an empty spaces devoid of cytoskeleton (dark areas). Arrows indicate areas of the F-actin periphery experiencing cortical disruptions. (C) Modeling cytoskeleton cages as diffusion barriers enhances secretory kinetics and sustained calcium levels. Calcium signals for a region between 0 to 50 nm from the membrane surface in a two parallelepiped model. The traces depicted correspond to three increasing porosities of the cytoskeleton: 0.01, 0.025 and 0.05.

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