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Synaptotagmin 5 regulates Ca2+-dependent Weibel-Palade body exocytosis in human endothelial cells.

Lenzi, C; Stevens, J; Osborn, D; Hannah, MJ; Bierings, R; Carter, T (2019) Synaptotagmin 5 regulates Ca2+-dependent Weibel-Palade body exocytosis in human endothelial cells. J Cell Sci, 132 (5). ISSN 1477-9137 https://doi.org/10.1242/jcs.221952
SGUL Authors: Carter, Thomas David Osborn, Daniel Peter Sayer

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Abstract

Elevations of intracellular free Ca2+ concentration ([Ca2+]i) are a potent trigger for Weibel-Palade body (WPB) exocytosis and secretion of von Willebrand factor (VWF) from endothelial cells; however, the identity of WPB-associated Ca2+-sensors involved in transducing acute increases in [Ca2+]i into granule exocytosis remains unknown. Here, we show that synaptotagmin 5 (SYT5) is expressed in human umbilical vein endothelial cells (HUVECs) and is recruited to WPBs to regulate Ca2+-driven WPB exocytosis. Western blot analysis of HUVECs identified SYT5 protein, and exogenously expressed SYT5-mEGFP localised almost exclusively to WPBs. shRNA-mediated knockdown of endogenous SYT5 (shSYT5) reduced the rate and extent of histamine-evoked WPB exocytosis and reduced secretion of the WPB cargo VWF-propeptide (VWFpp). The shSYT5-mediated reduction in histamine-evoked WPB exocytosis was prevented by expression of shRNA-resistant SYT5-mCherry. Overexpression of SYT5-EGFP increased the rate and extent of histamine-evoked WPB exocytosis, and increased secretion of VWFpp. Expression of a Ca2+-binding defective SYT5 mutant (SYT5-Asp197Ser-EGFP) mimicked depletion of endogenous SYT5. We identify SYT5 as a WPB-associated Ca2+ sensor regulating Ca2+-dependent secretion of stored mediators from vascular endothelial cells.

Item Type: Article
Additional Information: © 2019. Published by The Company of Biologists Ltd
Keywords: Ca2+, Endothelial, Exocytosis, Secretion, Synaptotagmin, Weibel–Palade body, 06 Biological Sciences, 11 Medical And Health Sciences, Developmental Biology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: J Cell Sci
ISSN: 1477-9137
Language: eng
Dates:
DateEvent
15 February 2019Published
18 January 2019Published Online
9 January 2019Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
MC_PC_13053Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 30659119
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/110515
Publisher's version: https://doi.org/10.1242/jcs.221952

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