File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1016/j.biocel.2015.02.003
- Scopus: eid_2-s2.0-84923221137
- PMID: 25681686
- WOS: WOS:000351796300007
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling
Title | PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling |
---|---|
Authors | |
Keywords | ErbB4 Neuritic elongation NRG3 Pro-neuronal survival PTPN21 |
Issue Date | 2015 |
Publisher | Pergamon. 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? |
Abstract | Although 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 Identifier | http://hdl.handle.net/10722/209788 |
ISSN | 2023 Impact Factor: 3.4 2023 SCImago Journal Rankings: 1.079 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Plani-Lam, JH | - |
dc.contributor.author | Chow, TC | - |
dc.contributor.author | Siu, KL | - |
dc.contributor.author | Chau, WH | - |
dc.contributor.author | Ng, MH | - |
dc.contributor.author | Bao, S | - |
dc.contributor.author | Ng, CT | - |
dc.contributor.author | Sham, PC | - |
dc.contributor.author | Shum, DKY | - |
dc.contributor.author | Jin, D | - |
dc.contributor.author | Song, Y | - |
dc.date.accessioned | 2015-05-18T03:22:51Z | - |
dc.date.available | 2015-05-18T03:22:51Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | The International Journal of Biochemistry & Cell Biology, 2015, v. 61, p. 53-62 | - |
dc.identifier.issn | 1357-2725 | - |
dc.identifier.uri | http://hdl.handle.net/10722/209788 | - |
dc.description.abstract | Although 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.language | eng | - |
dc.publisher | Pergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocel | - |
dc.relation.ispartof | The International Journal of Biochemistry & Cell Biology | - |
dc.subject | ErbB4 | - |
dc.subject | Neuritic elongation | - |
dc.subject | NRG3 | - |
dc.subject | Pro-neuronal survival | - |
dc.subject | PTPN21 | - |
dc.title | PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling | - |
dc.type | Article | - |
dc.identifier.email | Bao, S: shaine85@hku.hk | - |
dc.identifier.email | Sham, PC: pcsham@hku.hk | - |
dc.identifier.email | Shum, DKY: shumdkhk@hkucc.hku.hk | - |
dc.identifier.email | Jin, D: dyjin@hku.hk | - |
dc.identifier.email | Song, Y: songy@hku.hk | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.identifier.authority | Shum, DKY=rp00321 | - |
dc.identifier.authority | Jin, D=rp00452 | - |
dc.identifier.authority | Song, Y=rp00488 | - |
dc.identifier.doi | 10.1016/j.biocel.2015.02.003 | - |
dc.identifier.pmid | 25681686 | - |
dc.identifier.scopus | eid_2-s2.0-84923221137 | - |
dc.identifier.hkuros | 243090 | - |
dc.identifier.volume | 61 | - |
dc.identifier.spage | 53 | - |
dc.identifier.epage | 62 | - |
dc.identifier.isi | WOS:000351796300007 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1357-2725 | - |