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Article: PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling

TitlePTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling
Authors
Issue Date2015
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocel
Citation
The International Journal of Biochemistry & Cell Biology, 2015, v. 61, p. 53-62 How to Cite?
AbstractAlthough expression quantitative trait locus, eQTL, serves as an explicit indicator of gene-gene associations, challenges remain to disentangle the mechanisms by which genetic variations alter gene expression. Here we combined eQTL and molecular analyses to identify an association between two seemingly non-associated genes in brain expression data from BXD inbred mice, namely Ptpn21 and Nrg3. Using biotinylated receptor tracking and immunoprecipitation analyses, we determined that PTPN21 de-phosphorylates the upstream receptor tyrosine kinase ErbB4 leading to the up-regulation of its downstream signaling. Conversely, kinase-dead ErbB4 (K751R) or phosphatase-dead PTPN21 (C1108S) mutants impede PTPN21-dependent signaling. Furthermore, PTPN21 also induced Elk-1 activation in embryonic cortical neurons and a novel Elk-1 binding motif was identified in a region located 1919bp upstream of the NRG3 initiation codon. This enables PTPN21 to promote NRG3 expression through Elk-1, which provides a biochemical mechanism for the PTPN21-NRG3 association identified by eQTL. Biologically, PTPN21 positively influences cortical neuronal survival and, similar to Elk-1, it also enhances neuritic length. Our combined approaches show for the first time, a link between NRG3 and PTPN21 within a signaling cascade. This may explain why these two seemingly unrelated genes have previously been identified as risk genes for schizophrenia.
Persistent Identifierhttp://hdl.handle.net/10722/209788
ISSN
2015 Impact Factor: 3.905
2015 SCImago Journal Rankings: 2.003
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPlani-Lam, JH-
dc.contributor.authorChow, TC-
dc.contributor.authorSiu, KL-
dc.contributor.authorChau, WH-
dc.contributor.authorNg, MH-
dc.contributor.authorBao, S-
dc.contributor.authorNg, CT-
dc.contributor.authorSham, PC-
dc.contributor.authorShum, DKY-
dc.contributor.authorJin, D-
dc.contributor.authorSong, Y-
dc.date.accessioned2015-05-18T03:22:51Z-
dc.date.available2015-05-18T03:22:51Z-
dc.date.issued2015-
dc.identifier.citationThe International Journal of Biochemistry & Cell Biology, 2015, v. 61, p. 53-62-
dc.identifier.issn1357-2725-
dc.identifier.urihttp://hdl.handle.net/10722/209788-
dc.description.abstractAlthough expression quantitative trait locus, eQTL, serves as an explicit indicator of gene-gene associations, challenges remain to disentangle the mechanisms by which genetic variations alter gene expression. Here we combined eQTL and molecular analyses to identify an association between two seemingly non-associated genes in brain expression data from BXD inbred mice, namely Ptpn21 and Nrg3. Using biotinylated receptor tracking and immunoprecipitation analyses, we determined that PTPN21 de-phosphorylates the upstream receptor tyrosine kinase ErbB4 leading to the up-regulation of its downstream signaling. Conversely, kinase-dead ErbB4 (K751R) or phosphatase-dead PTPN21 (C1108S) mutants impede PTPN21-dependent signaling. Furthermore, PTPN21 also induced Elk-1 activation in embryonic cortical neurons and a novel Elk-1 binding motif was identified in a region located 1919bp upstream of the NRG3 initiation codon. This enables PTPN21 to promote NRG3 expression through Elk-1, which provides a biochemical mechanism for the PTPN21-NRG3 association identified by eQTL. Biologically, PTPN21 positively influences cortical neuronal survival and, similar to Elk-1, it also enhances neuritic length. Our combined approaches show for the first time, a link between NRG3 and PTPN21 within a signaling cascade. This may explain why these two seemingly unrelated genes have previously been identified as risk genes for schizophrenia.-
dc.languageeng-
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocel-
dc.relation.ispartofThe International Journal of Biochemistry & Cell Biology-
dc.titlePTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling-
dc.typeArticle-
dc.identifier.emailBao, S: shaine85@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailShum, DKY: shumdkhk@hkucc.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailSong, Y: songy@hku.hk-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityShum, DKY=rp00321-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authoritySong, Y=rp00488-
dc.identifier.doi10.1016/j.biocel.2015.02.003-
dc.identifier.pmid25681686-
dc.identifier.scopuseid_2-s2.0-84923221137-
dc.identifier.hkuros243090-
dc.identifier.volume61-
dc.identifier.spage53-
dc.identifier.epage62-
dc.identifier.isiWOS:000351796300007-
dc.publisher.placeUnited Kingdom-

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