Granuphilin modulates the exocytosis of secretory granules through interaction with syntaxin 1a.
Mol Cell Biol
; 22(15): 5518-26, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12101244
ABSTRACT
The molecular mechanism for the regulated exocytosis of dense-core granules in endocrine cells remains relatively uncharacterized compared to that of synaptic vesicles in neurons. A novel set of Rab and its effector, Rab27a/granuphilin, which is localized on insulin granules in pancreatic beta cells, was recently identified. Here we demonstrate that granuphilin directly binds to syntaxin 1a on the plasma membrane, and this interaction is regulated by Rab27a. Granuphilin shows affinity to syntaxin 1a with a closed conformation but not to mutant syntaxin 1a, which adopts an open conformation constitutively. Overexpression of granuphilin significantly enhances basal insulin secretion but profoundly inhibits high K(+)-induced insulin secretion. The effect of granuphilin on insulin secretion was impaired by its mutation that disrupts the binding to either Rab27a or syntaxin 1a. Thus, granuphilin is the first regulator in the exocytotic pathway that functions by directly connecting two critical vesicle transport proteins, Rab and SNARE.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Ilhotas Pancreáticas
/
Vesículas Secretórias
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Proteínas de Transporte Vesicular
/
Exocitose
/
Antígenos de Superfície
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Japão