Synaptotagmin-like protein 1 interacts with the GTPase-activating protein Rap1GAP2 and regulates dense granule secretion in platelets

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dc.contributor.authorNeumüller, Olga
dc.contributor.authorHoffmeister, Meike
dc.contributor.authorBabica, Jan
dc.contributor.authorGegenbauer, Kristina
dc.contributor.authorSmolenski, Albert P.
dc.contributor.authoret al.
dc.date.accessioned2014-09-08T08:02:48Z
dc.date.available2014-09-08T08:02:48Z
dc.date.copyright2009 The American Society of Hematologyen
dc.date.issued2009-08-13
dc.identifier.citationBlooden
dc.identifier.urihttp://hdl.handle.net/10197/5848
dc.description.abstractThe small guanine-nucleotide–binding protein Rap1 plays a key role in platelet aggregation and hemostasis, and we recently identified Rap1GAP2 as the only GTPase-activating protein of Rap1 in platelets. In search of Rap1GAP2-associated proteins, we performed yeast-2-hybrid screening and found synaptotagmin-like protein 1 (Slp1) as a new binding partner. We confirmed the interaction of Rap1GAP2 and Slp1 in transfected COS-1 and HeLa cells and at endogenous level in human platelets. Mapping studies showed that Rap1GAP2 binds through amino acids T524-K525-X-T527 within its C-terminus to the C2A domain of Slp1. Slp1 contains a Rab27-binding domain, and we demonstrate that Rap1GAP2, Slp1, and Rab27 form a trimeric complex in transfected cells and in platelets. Purified Slp1 dose-dependently decreased dense granule secretion in streptolysin-O–permeabilized platelets stimulated with calcium or guanosine 5′-O-[gamma-thio] triphosphate. The isolated C2A domain of Slp1 had a stimulatory effect on granule secretion and reversed the inhibitory effect of full-length Slp1. Purified Rap1GAP2 augmented dense granule secretion of permeabilized platelets, whereas deletion of the Slp1-binding TKXT motif abolished the effect of Rap1GAP2. We conclude that Slp1 inhibits dense granule secretion in platelets and that Rap1GAP2 modulates secretion by binding to Slp1.en
dc.description.sponsorshipScience Foundation Irelanden
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.subjectRap1GAP2en
dc.subjectPlatelet aggregationen
dc.subjectPlatelet hemostasisen
dc.titleSynaptotagmin-like protein 1 interacts with the GTPase-activating protein Rap1GAP2 and regulates dense granule secretion in plateletsen
dc.title.alternativeSlp1 regulates platelet secretionen
dc.typeJournal Articleen
dc.internal.authorcontactotheralbert.smolenski@ucd.ie
dc.internal.availabilityFull text availableen
dc.statusPeer revieweden
dc.identifier.volume114en
dc.identifier.issue7en
dc.identifier.startpage1396en
dc.identifier.endpage1404en
dc.identifier.doi10.1182/blood-2008-05-155234-
dc.neeo.contributorNeumüller|Olga|aut|-
dc.neeo.contributorHoffmeister|Meike|aut|-
dc.neeo.contributorBabica|Jan|aut|-
dc.neeo.contributorGegenbauer|Kristina|aut|-
dc.neeo.contributorSmolenski|Albert P.|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipDeutsche Forschungsgemeinschaften
dc.description.othersponsorshipExcellence Cluster Cardio-Pulmonary Systemen
dc.internal.rmsid129234916
dc.date.updated2014-08-13T10:53:05Z
item.grantfulltextopen-
item.fulltextWith Fulltext-
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