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

TitleNetrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B
Authors
Issue Date2008
Citation
Nature Cell Biology, 2008, v. 10, n. 6, p. 698-706 How to Cite?
AbstractNetrins, 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.
Persistent Identifierhttp://hdl.handle.net/10722/225046
ISSN
2015 Impact Factor: 18.699
2015 SCImago Journal Rankings: 14.131

 

DC FieldValueLanguage
dc.contributor.authorTang, Xiaoling-
dc.contributor.authorJang, Sung Wuk-
dc.contributor.authorOkada, Masashi-
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorFeng, Yue-
dc.contributor.authorLiu, Yu-
dc.contributor.authorLuo, Shi Wen-
dc.contributor.authorHong, Yan-
dc.contributor.authorRama, Nicolas-
dc.contributor.authorXiong, Wen Cheng-
dc.contributor.authorMehlen, Patrick-
dc.contributor.authorYe, Keqiang-
dc.date.accessioned2016-04-18T11:16:36Z-
dc.date.available2016-04-18T11:16:36Z-
dc.date.issued2008-
dc.identifier.citationNature Cell Biology, 2008, v. 10, n. 6, p. 698-706-
dc.identifier.issn1465-7392-
dc.identifier.urihttp://hdl.handle.net/10722/225046-
dc.description.abstractNetrins, 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.-
dc.languageeng-
dc.relation.ispartofNature Cell Biology-
dc.titleNetrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ncb1732-
dc.identifier.pmid18469807-
dc.identifier.scopuseid_2-s2.0-44649197812-
dc.identifier.volume10-
dc.identifier.issue6-
dc.identifier.spage698-
dc.identifier.epage706-

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