Pericentrosomal Targeting of Rab6 Secretory Vesicles by Bicaudal-D-related Protein 1 (BICDR-1) Regulates Neuritogenesis

EMBO J. 2010 May 19;29(10):1637-51. doi: 10.1038/emboj.2010.51. Epub 2010 Apr 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Animals
  • Brain / metabolism
  • COS Cells
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Centrosome / ultrastructure*
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Kidney / metabolism
  • Kinesin / chemistry
  • Models, Biological
  • Neurons / metabolism
  • Neurons / pathology*
  • Zebrafish
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • BICD1 protein, human
  • Bicdl1 protein, mouse
  • Cytoskeletal Proteins
  • KIF1C protein, human
  • Rab6 protein
  • Kinesin
  • rab GTP-Binding Proteins