Journal
EMBO JOURNAL
Volume 29, Issue 10, Pages 1637-1651Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.51
Keywords
centrosome; dynein motor proteins; neuronal development; Rab GTPase; secretory trafficking
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Funding
- The Prinses Beatrix Fonds
- Netherlands Organization for Health Research and Development (ZonMw-VIDI)
- Netherlands Organization for Scientific Research (NWO-ALW VICI)
- Netherlands Organization for Health Research and Development (ZonMw-TOP)
- Netherlands Organization for Scientific Research (NWO-ALW, NWO-ECHO)
- Netherlands Organization for Health Research and Development (ZonMw-VIDI, ZonMw-TOP)
- European Science Foundation (European Young Investigators (EURYI)
- EMBO Young Investigators Program (YIP)
- Human Frontier Science Program Career Development Award (HFSP-CDA)
- Grants-in-Aid for Scientific Research [20113006] Funding Source: KAKEN
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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. BICDR1 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. The EMBO Journal (2010) 29,1637-1651. doi: 10.1038/emboj.2010.51; Published online 1 April 2010
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