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Synaptotagmin-like protein 4 and Rab8 interact and increase dense granule release in platelets
Alternative Title
Role of Slp4 and Rab8 in dense granule release
Author(s)
Date Issued
2013-01-27
Date Available
2014-09-23T07:33:58Z
Abstract
Background: Platelets are highly specialized cells that regulate hemostasis and thrombosis in the vasculature. Upon activation, platelets release various granules that impact on platelets, the coagulation system, other blood cells and the vessel wall; however, the mechanisms controlling granule release are only partially known. We have shown previously that synaptotagmin-like protein (Slp)1 decreases dense granule release in platelets. Objectives: To determine the role of other Slps and their binding partners on platelet dense granule release. Methods: RT-PCR and immunoblotting were used to identify Slps in human platelets. Interaction between Slp4 and Rab8 was investigated with pull-down assays, coimmunoprecipitation, and confocal microscopy. Secretion assays on permeabilized platelets were performed to investigate the effects of Slp4 and Rab8 on dense granule release. Results: Slp4 mRNA and protein are expressed in human platelets. Slp4 interacts with Rab8 in transfected cells and at endogenous protein levels in platelets. We mapped the Rab interaction site to the Slp-homology domain of Slp4, and showed preferential binding of Slp4 to the GTP-bound form of Rab8. Live microscopy showed colocalization of green fluorescent protein-Slp4 and mCherry-Rab8 at the plasma membrane of transfected cells. Endogenous platelet Slp4 and Rab8 colocalized in the center of activated platelets, where granule secretion takes place. Secretion assays revealed that Slp4 and Rab8 enhance dense granule release and that the Slp4 effect is dependent on Rab8 binding. Conclusions: Slp4 and Rab8 are expressed and interact in human platelets, and might be involved in dense granule release.
Sponsorship
Science Foundation Ireland
Type of Material
Journal Article
Publisher
Wiley
Journal
Journal of Thrombosis and Haemostasis
Volume
11
Issue
1
Start Page
161
End Page
168
Copyright (Published Version)
2012 International Society on Thrombosis and Haemostasis
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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