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PMID:19196994

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Citation

Liu, G, Li, W, Wang, L, Kar, A, Guan, KL, Rao, Y and Wu, JY (2009) DSCAM functions as a netrin receptor in commissural axon pathfinding. Proc. Natl. Acad. Sci. U.S.A. 106:2951-6

Abstract

Down syndrome cell adhesion molecule (DSCAM) is required for axon guidance and dendrite arborization. How DSCAM functions in vertebrates is not well understood. Here we show that DSCAM is expressed on commissural axons and interacts with Netrin-1, a prototypical guidance cue for commissural axons. The knockdown of DSCAM by specific siRNA or blockage of DSCAM signaling by overexpression of a mutant lacking its intracellular domain inhibits netrin-induced axon outgrowth and commissural axon turning in vitro. SiRNA-mediated knockdown of DSCAM in ovo causes defects in commissural axon projection and pathfinding. In transfected cells, DSCAM by itself, in the absence of DCC, is capable of mediating netrin signaling in activating phosphorylation of Fyn and Pak1. These findings demonstrate an essential role of vertebrate DSCAM in axon guidance, indicating that DSCAM functions as a receptor of netrin-1. Our data suggest previously unexpected complexity in receptors that mediate vertebrate netrin signaling.

Links

PubMed PMC2650370 Online version:10.1073/pnas.0811083106

Keywords

Animals; Axons; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cell Adhesion Molecules/physiology; Cell Line; Chick Embryo; Gene Knockdown Techniques; Humans; Immunoprecipitation; Nerve Growth Factors/metabolism; Phosphorylation; RNA, Small Interfering; Receptors, Cell Surface/physiology; Signal Transduction; Tumor Suppressor Proteins/metabolism

Significance

Annotations

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

HUMAN:DSCAM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O95631

F

Seeded From UniProt

complete

HUMAN:NET1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60469

F

Seeded From UniProt

complete

MOUSE:DSCAM

located_in

GO:0030426: growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DSCAM

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DSCAM

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DSCAM

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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