Unc5B associates with LARG to mediate the action of repulsive guidance molecule

Katsuhiko Hata, Kozo Kaibuchi, Shinobu Inagaki, Toshihide Yamashita

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

Neuronal axons are guided by attractive and repulsive cues in their local environment. Because the repulsive guidance molecule A (RGMa) was originally identified as an axon repellent in the visual system, diverse functions in the developing and adult central nervous system have been ascribed to it. RGMa binding to its receptor neogenin induces RhoA activation, leading to inhibitory/repulsive behavior and collapse of the neuronal growth cone. However, the precise mechanisms that regulate RhoA activation are poorly understood. In this study, we show that Unc5B, a member of the netrin receptor family, interacts with neogenin as a coreceptor for RGMa. Moreover, leukemia-associated guanine nucleotide exchange factor (LARG) associates with Unc5B to transduce the RhoA signal. Focal adhesion kinase (FAK) is involved in RGMa-induced tyrosine phosphorylation of LARG as well as RhoA activation. These fiNdings uncover the molecular basis for diverse functions mediated by RGMa.

Original languageEnglish
Pages (from-to)737
Number of pages1
JournalJournal of Cell Biology
Volume184
Issue number5
DOIs
Publication statusPublished - 09-03-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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