TY - JOUR
T1 - Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis
AU - Schlager, Max A.
AU - Kapitein, Lukas C.
AU - Grigoriev, Ilya
AU - Burzynski, Grzegorz M.
AU - Wulf, Phebe S.
AU - Keijzer, Nanda
AU - De Graaff, Esther
AU - Fukuda, Mitsunori
AU - Shepherd, Iain T.
AU - Akhmanova, Anna
AU - Hoogenraad, Casper C.
PY - 2010/5/19
Y1 - 2010/5/19
N2 - 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.
AB - 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.
KW - Centrosome
KW - Dynein motor proteins
KW - Neuronal development
KW - Rab GTPase
KW - Secretory trafficking
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U2 - 10.1038/emboj.2010.51
DO - 10.1038/emboj.2010.51
M3 - Article
C2 - 20360680
AN - SCOPUS:77952574451
SN - 0261-4189
VL - 29
SP - 1637
EP - 1651
JO - EMBO Journal
JF - EMBO Journal
IS - 10
ER -