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dc.contributor.authorPetrie, Matt
dc.contributor.authorEsquibel, Joseph
dc.contributor.authorKabachinski, Greg
dc.contributor.authorMaciuba, Stephanie
dc.contributor.authorTakahashi, Hirohide
dc.contributor.authorEdwardson, Michael
dc.contributor.authorMartin, Thomas FJ
dc.date.accessioned2018-09-20T12:06:21Z
dc.date.available2018-09-20T12:06:21Z
dc.date.issued2016-09-30
dc.identifier.issn0021-9258
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280526
dc.description.abstractNeurotransmitters and peptide hormones are secreted by regulated vesicle exocytosis. CAPS (also known as CADPS) is a 145-kDa cytosolic and peripheral membrane protein required for vesicle docking and priming steps that precede Ca2+-triggered vesicle exocytosis. CAPS binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and SNARE proteins and is proposed to promote SNARE protein complex assembly for vesicle docking and priming. We characterized purified soluble CAPS as mainly monomer in equilibrium with small amounts of dimer. However, the active form of CAPS bound to PC12 cell membranes or to liposomes containing PI(4,5)P2 and Q-SNARE proteins was mainly dimer. CAPS dimer formation required its C2 domain based on mutation or deletion studies. Moreover, C2 domain mutations or deletions resulted in a loss of CAPS function in regulated vesicle exocytosis, indicating that dimerization is essential for CAPS function. Comparison of the CAPS C2 domain to a structurally defined Munc13-1 C2A domain dimer revealed conserved residues involved in CAPS dimerization. We conclude that CAPS functions as a C2 domain-mediated dimer in regulated vesicle exocytosis. The unique tandem C2-PH domain of CAPS may serve as a PI(4,5)P2-triggered switch for dimerization. CAPS dimerization may be coupled to oligomeric SNARE complex assembly for vesicle docking and priming.
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSNARE proteins
dc.subjectdimerization
dc.subjectexocytosis
dc.subjectinositol phospholipid
dc.subjectvesicles
dc.subjectAnimals
dc.subjectCalcium-Binding Proteins
dc.subjectExocytosis
dc.subjectNerve Tissue Proteins
dc.subjectPC12 Cells
dc.subjectPhosphatidylinositol 4,5-Diphosphate
dc.subjectProtein Domains
dc.subjectProtein Multimerization
dc.subjectQ-SNARE Proteins
dc.subjectRats
dc.subjectSecretory Vesicles
dc.titleThe Vesicle Priming Factor CAPS Functions as a Homodimer via C2 Domain Interactions to Promote Regulated Vesicle Exocytosis.
dc.typeArticle
prism.endingPage21270
prism.issueIdentifier40
prism.publicationDate2016
prism.publicationNameJ Biol Chem
prism.startingPage21257
prism.volume291
dc.identifier.doi10.17863/CAM.27895
rioxxterms.versionofrecord10.1074/jbc.M116.728097
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-09-30
dc.identifier.eissn1083-351X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2016-08-15


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International