|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.
|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|
|PubMed:||20360680 Full text @ EMBO J.|
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. (2010) Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. The EMBO journal. 29(10):1637-1651.
ABSTRACTMembrane 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.