Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis

Max Schlager, Lukas Kapitein, I Grigoriev, GM Burzynski, PS Wulf, Nanda Keijzer, Esther Graaff, M Fukuda, IT Shepherd, Anna Akhmanova, CC Hoogenraad

Research output: Contribution to journalArticleAcademicpeer-review

110 Citations (Scopus)

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. 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
Original languageUndefined/Unknown
Pages (from-to)1637-1651
Number of pages15
JournalEMBO Journal
Volume29
Issue number10
DOIs
Publication statusPublished - 2010

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