ZFIN ID: ZDB-PUB-100408-14
Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis
Schlager, M.A., Kapitein, L.C., Grigoriev, I., Burzynski, G.M., Wulf, P.S., Keijzer, N., de Graaff, E., Fukuda, M., Shepherd, I.T., Akhmanova, A., and Hoogenraad, C.C.
Date: 2010
Source: The EMBO journal   29(10): 1637-1651 (Journal)
Registered Authors: Shepherd, Iain T.
Keywords: centrosome, dynein motor proteins, neuronal development, Rab GTPase, secretory trafficking
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*
PubMed: 20360680 Full text @ EMBO J.
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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.
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