title: The roles of Rab27 and its effectors in the regulated secretory pathways.
abstract: Regulated secretory pathways are highly developed in multicellular organisms as a means of intercellular communication. Each of these pathways harbors unique store organelles, such as granules in endocrine and exocrine tissues and melanosomes in melanocytes. It has recently been shown that the monomeric GTPase Rab27 subfamily regulates the exocytosis of these cell-specific store organelles. Furthermore, genetic alterations of Rab27a cause Griscelli syndrome in humans that manifests as pigmentary dilution of the skin and the hair and variable immunodeficiency due to defects in the transport of melanosomes in melanocytes and lytic granules in cytotoxic T-lymphocytes. Rab27 acts through organelle-specific effector proteins, such as granuphilin in pancreatic beta cells and melanophilin in melanocytes. The Rab27 and effector complex then interacts with proteins that are essential for membrane transport and fusion, such as syntaxin 1a and Munc18-1 for granuphilin and myosin Va for melanophilin. Genome information suggests that other putative Rab27 effector proteins, tentatively termed as exophilins or Slp/Slac2, are predicted to exist because these proteins share the conserved N-terminal Rab27-binding domain and show Rab27-binding activity in vitro or when overexpressed in cell lines. These findings suggest that the Rab27 subfamily regulates various exocytotic pathways using multiple organelle-specific effector proteins.
authors.affiliation: Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan. tizumi@showa.gunma-u.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Izumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Gomi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasai
authors.forename: Shin
authors.initials: S
authors.lastname: Mizutani
authors.forename: Seiji
authors.initials: S
authors.lastname: Torii
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D022142:Secretory Vesicles / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492410:MLPH protein, human; C512779:SYTL4 protein, human; D033921:Vesicular Transport Proteins; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins