Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis

Max A. Schlager, Lukas C. Kapitein, Ilya Grigoriev, Grzegorz M. Burzynski, Phebe S. Wulf, Nanda Keijzer, Esther De Graaff, Mitsunori Fukuda, Iain T. Shepherd, Anna Akhmanova, Casper C. Hoogenraad

    Research output: Contribution to journalArticlepeer-review

    94 Citations (Scopus)

    Abstract

    Membrane and secretory trafficking are essential for proper neuronal development. However, the molecular mechanisms that organize secretory trafficking are poorly understood. Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. BICDR-1 expression is high during early neuronal development and strongly declines during neurite outgrowth. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.

    Original languageEnglish
    Pages (from-to)1637-1651
    Number of pages15
    JournalEMBO Journal
    Volume29
    Issue number10
    DOIs
    Publication statusPublished - 2010 May 19

    Keywords

    • Centrosome
    • Dynein motor proteins
    • Neuronal development
    • Rab GTPase
    • Secretory trafficking

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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