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http://purl.uniprot.org/citations/12590134http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12590134http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12590134http://www.w3.org/2000/01/rdf-schema#comment"Slp4-a (synaptotagmin-like protein 4-a)/granuphilin-a is specifically localized on dense-core vesicles in PC12 cells and negatively controls dense-core vesicle exocytosis through specific interaction with Rab27A via the N-terminal Slp homology domain (SHD) (Fukuda, M., Kanno, E., Saegusa, C., Ogata, Y., and Kuroda, T. S. (2002) J. Biol. Chem. 277, 39673-39678). However, the mechanism of the inhibition by Slp4-a has never been elucidated at the molecular level and is still a matter of controversy. In this study, I discovered an unexpected biochemical property of Slp4-a, that Slp4-a, but not other Rab27 effectors reported thus far, is capable of interacting with both Rab27A(T23N), a dominant negative form that mimics the GDP-bound form, and Rab27A(Q78L), a dominant active form that mimics the GTP-bound form, whereas Slp4-a specifically recognizes the GTP-bound form of Rab3A and Rab8A and does not recognize their GDP-bound form. I show by deletion and mutation analyses that the TGDWFY sequence in SHD2 is essential for Rab27A(T23N) binding, whereas SHD1 is involved in Rab27A(Q78L) binding. I further show by immunoprecipitation and cotransfection assays that Munc18-1, but not syntaxin IA, directly interacts with the C-terminal domain of Slp4-a in a Rab27A-independent manner. Expression of Slp4-a mutants that lack Rab27A(T23N) binding activity (i.e. specific binding to Rab27A(Q78L)) completely reverses the inhibitory effect of the wild-type Slp4-a on high KCl-dependent neuropeptide Y secretion in PC12 cells. The results strongly indicate that interaction of Slp4-a with the GDP-bound form of Rab27A, not with syntaxin IA or Munc18-1, is the primary reason that Slp4-a expression inhibits dense core vesicle exocytosis in PC12 cells."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m213090200"xsd:string
http://purl.uniprot.org/citations/12590134http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m213090200"xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/author"Fukuda M."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/author"Fukuda M."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/pages"15390-15396"xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/pages"15390-15396"xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/title"Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/title"Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells."xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12590134http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12590134http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12590134
http://purl.uniprot.org/citations/12590134http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12590134
http://purl.uniprot.org/citations/12590134http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12590134
http://purl.uniprot.org/citations/12590134http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12590134
http://purl.uniprot.org/uniprot/Q0VAV2http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/12590134
http://purl.uniprot.org/uniprot/P55258http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/12590134
http://purl.uniprot.org/uniprot/Q9R0Q1http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/12590134
http://purl.uniprot.org/uniprot/Q80T23http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/12590134