PUBLICATION
Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis
- Authors
- 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.
- ID
- ZDB-PUB-100408-14
- 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
-
- COS Cells
- Kinesins/chemistry
- Centrosome/ultrastructure*
- rab GTP-Binding Proteins/metabolism*
- Models, Biological
- PubMed
- 20360680 Full text @ EMBO J.
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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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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