RGD Reference Report - Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B. - Rat Genome Database

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Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B.

Authors: Tang, X  Jang, SW  Okada, M  Chan, CB  Feng, Y  Liu, Y  Luo, SW  Hong, Y  Rama, N  Xiong, WC  Mehlen, P  Ye, K 
Citation: Tang X, etal., Nat Cell Biol. 2008 Jun;10(6):698-706. doi: 10.1038/ncb1732. Epub 2008 May 11.
RGD ID: 8553892
Pubmed: PMID:18469807   (View Abstract at PubMed)
PMCID: PMC2839190   (View Article at PubMed Central)
DOI: DOI:10.1038/ncb1732   (Journal Full-text)

Netrins, a family of secreted molecules, have critical functions in axon guidance and cell migration during neuronal development. In addition to its role as a chemotropic molecule, netrin-1 also acts as a survival factor. Both UNC5 (that is, UNC5A, UNC5B, UNC5C or UNC5D) and DCC are transmembrane receptors for netrin-1 (Refs 8, 9). In the absence of netrin-1, DCC and UNC5 act as dependence receptors and trigger apoptosis. However, how netrin-1 suppresses the apoptotic activity of the receptors remains elusive. Here we show that netrin-1 induces interaction of UNC5B with the brain-specific GTPase PIKE-L. This interaction triggers the activation of PtdIns-3-OH kinase signalling, prevents UNC5B's pro-apoptotic activity and enhances neuronal survival. Moreover, this process relies strongly on Fyn because PIKE-L is tyrosine phosphorylated in response to netrin-1, and the netrin-1-mediated interaction of UNC5B with PIKE-L is inhibited in Fyn-null mice. Thus, PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Agap2  (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2)
Dcc  (DCC netrin 1 receptor)
Fyn  (FYN proto-oncogene, Src family tyrosine kinase)
Unc5b  (unc-5 netrin receptor B)


Additional Information