title: Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis.
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.
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Max A
authors.initials: MA
authors.lastname: Schlager
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Burzynski
authors.forename: Phebe S
authors.initials: PS
authors.lastname: Wulf
authors.forename: Nanda
authors.initials: N
authors.lastname: Keijzer
authors.forename: Esther
authors.initials: E
authors.lastname: de Graaff
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Iain T
authors.initials: IT
authors.lastname: Shepherd
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D018385:Centrosome / Q000648:ultrastructure*; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D015027:Zebrafish; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C109571:BICD1 protein, human; C550010:Bicdl1 protein, mouse; D003598:Cytoskeletal Proteins; C114063:KIF1C protein, human; C094135:Rab6 protein; D016547:Kinesins; D020691:rab GTP-Binding Proteins