Rab27 Effectors, Pleiotropic Regulators in Secretory Pathways

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    109 Citations (Scopus)

    Abstract

    Rab27, a member of the small GTPase Rab family, is widely conserved in metazoan, and two Rab27 isoforms, Rab27A and Rab27B, are present in vertebrates. Rab27A was the first Rab protein whose dysfunction was found to cause a human hereditary disease, type 2 Griscelli syndrome, which is characterized by silvery hair and immunodeficiency. The discovery in the 21st century of three distinct types of mammalian Rab27A effectors [synaptotagmin-like protein (Slp), Slp homologue lacking C2 domains (Slac2), and Munc13-4] that specifically bind active Rab27A has greatly accelerated our understanding not only of the molecular mechanisms of Rab27Amediated membrane traffic (e.g. melanosome transport and regulated secretion) but of the symptoms of Griscelli syndrome patients at the molecular level. Because Rab27B is widely expressed in various tissues together with Rab27A and has been found to have the ability to bind all of the Rab27A effectors that have been tested, Rab27A and Rab27B were initially thought to function redundantly by sharing common Rab27 effectors. However, recent evidence has indicated that by interacting with different Rab27 effectors Rab27A and Rab27B play different roles in special types of secretion (e.g. exosome secretion and mast cell secretion) even within the same cell type. In this review article, I describe the current state of our understanding of the functions of Rab27 effectors in secretory pathways.

    Original languageEnglish
    Pages (from-to)949-963
    Number of pages15
    JournalTraffic
    Volume14
    Issue number9
    DOIs
    Publication statusPublished - 2013 Sep

    Keywords

    • Membrane traffic
    • Munc13-4
    • Rab27 effector
    • Secretory pathway
    • Slac2
    • Small GTPase
    • Synaptotagminlike protein (Slp)

    ASJC Scopus subject areas

    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics
    • Cell Biology

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