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PMID:20360680

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Citation

Schlager, MA, Kapitein, LC, Grigoriev, I, Burzynski, GM, Wulf, PS, Keijzer, N, de Graaff, E, Fukuda, M, Shepherd, IT, Akhmanova, A and Hoogenraad, CC (2010) Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 29:1637-51

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.

Links

PubMed PMC2876961 Online version:10.1038/emboj.2010.51

Keywords

Adaptor Proteins, Signal Transducing/metabolism; Adaptor Proteins, Vesicular Transport/metabolism; Animals; Brain/metabolism; COS Cells; Cell Differentiation; Cell Membrane/metabolism; Centrosome/ultrastructure; Cercopithecus aethiops; Cytoskeletal Proteins/metabolism; Humans; Kidney/metabolism; Kinesin/chemistry; Models, Biological; Neurons/metabolism; Neurons/pathology; Zebrafish; rab GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BICL1

enables

GO:0034452: dynactin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BICL1

located_in

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BICL1

involved_in

GO:0031175: neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BICL1

enables

GO:0031267: small GTPase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BICL1

involved_in

GO:0055107: Golgi to secretory granule transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BICL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43896

F

Seeded From UniProt

complete

MOUSE:BICL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35279

F

Seeded From UniProt

complete

MOUSE:BICL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P61294

F

Seeded From UniProt

complete

HUMAN:KIF1C

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A0JNT9

F

Seeded From UniProt

complete

DANRE:BICL1

involved_in

GO:0001654: eye development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:BICL1

involved_in

GO:0007420: brain development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100609-5,ZFIN:ZDB-MRPHLNO-100609-6

P

Seeded From UniProt

complete

DANRE:BICL1

involved_in

GO:0031076: embryonic camera-type eye development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-100609-5,ZFIN:ZDB-MRPHLNO-100609-6

P

Seeded From UniProt

complete

DANRE:BICL1

involved_in

GO:0010977: negative regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

RefSeq:NP_001074277.1

P

Seeded From UniProt

complete

DANRE:BICL1

involved_in

GO:0047496: vesicle transport along microtubule

ECO:0000316: genetic interaction evidence used in manual assertion

RefSeq:NP_001074277.1

P

Seeded From UniProt

complete

MOUSE:RAB6A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A0JNT9

F

Seeded From UniProt

complete

MOUSE:RAB6A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q921C5

F

Seeded From UniProt

complete

MOUSE:RAB6B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A0JNT9

F

Seeded From UniProt

complete

MOUSE:BICL2

enables

GO:0031267: small GTPase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BICD2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35279

F

Seeded From UniProt

complete


See also

References

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