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

• Max A Schlager ^[3] ; Lukas C Kapitein ^[3] ; Ilya Grigoriev ^[4] ; Grzegorz M Burzynski ^[1] ; Phebe S Wulf ^[3] ; Nanda Keijzer ^[3] ; Esther de Graaff ^[5] ; Mitsunori Fukuda ^[2] ; Iain T Shepherd ^[1] ; Anna Akhmanova ^[4] ; Casper C Hoogenraad ^[3]
  1. [1] Emory University

     Emory University

     Estados Unidos

     
  2. [2] Tohoku University

     Tohoku University

     Aoba-ku, Japón

     
  3. [3] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands
  4. [4] Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
  5. [5] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 10, 2010, págs. 1637-1651
• Idioma: inglés
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• Resumen

  • 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.