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Synaptotagmin-like protein 4 and rab8 interact and increase dense granule release in platelets.
MedLine Citation:
PMID:  23140275     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Platelets are highly specialized cells which regulate haemostasis and thrombosis in the vasculature. Upon activation platelets release various granules which impact on platelets, the coagulation system, other blood cells and on the vessel wall, however the mechanisms controlling granule release are only partially known. We have shown previously that synaptotagmin-like protein 1 (Slp1) decreases dense granule release in platelets. Objectives: To determine the role of other synaptotagmin-like proteins and their binding partners on platelet dense granule release. Methods: RT-PCR and immunoblot were used to identify Slps in human platelets. Interaction between Slp4 and Rab8 was investigated by pull-down assay, co-immunoprecipitation and by 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 SHD domain of Slp4 and we show preferential binding of Slp4 to the GTP-bound form of Rab8. Live microscopy showed co-localization of GFP-Slp4 and mCherry-Rab8 at the plasma membrane of transfected cells. Endogenous platelet Slp4 and Rab8 co-localized in the center of activated platelets where granule secretion takes place. Secretion assays revealed that Slp4 and Rab8 enhance dense granule release and we show 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. © 2012 International Society on Thrombosis and Haemostasis.
Authors:
A Hampson; A O'Connor; A Smolenski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-12
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Affiliation:
UCD Conway Institute, UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
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