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
-
- 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
- Kinesins/chemistry
- Models, Biological
- Neurons/metabolism
- Neurons/pathology*
- Zebrafish
- rab GTP-Binding Proteins/metabolism*
- PubMed
- 20360680 Full text @ EMBO J.
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping