Mammalian exocyst complex is required for the docking step of insulin vesicle exocytosis

Tsuboi, T., Ravier, M.A., Xie, H., Ewart, M.-A., Gould, G.W. , Baldwin, S.A. and Rutter, G.A. (2005) Mammalian exocyst complex is required for the docking step of insulin vesicle exocytosis. Journal of Biological Chemistry, 280(27), pp. 25565-25570. (doi:10.1074/jbc.M501674200)

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Abstract

Glucose stimulates insulin secretion from pancreatic β cells by inducing the recruitment and fusion of insulin vesicles to the plasma membrane. However, little is currently known about the mechanism of the initial docking or tethering of insulin vesicles prior to fusion. Here, we examined the role of the SEC6-SEC8 (exocyst) complex, implicated in trafficking of secretory vesicles to fusion sites in the plasma membrane in yeast and in regulating glucose-stimulated insulin secretion from pancreatic MIN6 β cells. We show first that SEC6 is concentrated on insulin-positive vesicles, whereas SEC5 and SEC8 are largely confined to the cytoplasm and the plasma membrane, respectively. Overexpression of truncated, dominant-negative SEC8 or SEC10 mutants decreased the number of vesicles at the plasma membrane, whereas expression of truncated SEC6 or SEC8 inhibited overall insulin secretion. When single exocytotic events were imaged by total internal reflection fluorescence microscopy, the fluorescence of the insulin surrogate, neuropeptide Y-monomeric red fluorescent protein brightened, diffused, and then vanished with kinetics that were unaffected by overexpression of truncated SEC8 or SEC10. Together, these data suggest that the exocyst complex serves to selectively regulate the docking of insulin-containing vesicles at sites of release close to the plasma membrane.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gould, Professor Gwyn and Ewart, Dr Marie-Ann
Authors: Tsuboi, T., Ravier, M.A., Xie, H., Ewart, M.-A., Gould, G.W., Baldwin, S.A., and Rutter, G.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:03 May 2005

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