File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Cyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis

TitleCyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis
Authors
Issue Date2015
PublisherThe American Society for Biochemistry and Molecular Biology,. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2015, v. 290 n. 23, p. 14637-14646 How to Cite?
AbstractThe maturation and maintenance of dendritic spines depends on neuronal activity and protein synthesis. One potential mechanism involves mammalian target of rapamycin, which promotes protein synthesis through phosphorylation of eIF4E-binding protein and p70 ribosomal S6 kinase 1 (S6K). Upon extracellular stimulation, mammalian target of rapamycin phosphorylates S6K at Thr-389. S6K also undergoes phosphorylation at other sites, including four serine residues in the autoinhibitory domain. Despite extensive biochemical studies, the importance of phosphorylation in the autoinhibitory domain in S6K function remains unresolved, and its role has not been explored in the cellular context. Here we demonstrated that S6K in neuron was phosphorylated at Ser-411 within the autoinhibitory domain by cyclin-dependent kinase 5. Ser-411 phosphorylation was regulated by neuronal activity and brain-derived neurotrophic factor (BDNF). Knockdown of S6K in hippocampal neurons by RNAi led to loss of dendritic spines, an effect that mimics neuronal activity blockade by tetrodotoxin. Notably, coexpression of wild type S6K, but not the phospho-deficient S411A mutant, could rescue the spine defects. These findings reveal the importance of cyclin-dependent kinase 5-mediated phosphorylation of S6K at Ser-411 in spine morphogenesis driven by BDNF and neuronal activity.
Persistent Identifierhttp://hdl.handle.net/10722/214976
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLai, KO-
dc.contributor.authorLiang, Z-
dc.contributor.authorFei, E-
dc.contributor.authorHuang, H-
dc.contributor.authorIp, NY-
dc.date.accessioned2015-08-21T12:15:47Z-
dc.date.available2015-08-21T12:15:47Z-
dc.date.issued2015-
dc.identifier.citationJournal of Biological Chemistry, 2015, v. 290 n. 23, p. 14637-14646-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/214976-
dc.description.abstractThe maturation and maintenance of dendritic spines depends on neuronal activity and protein synthesis. One potential mechanism involves mammalian target of rapamycin, which promotes protein synthesis through phosphorylation of eIF4E-binding protein and p70 ribosomal S6 kinase 1 (S6K). Upon extracellular stimulation, mammalian target of rapamycin phosphorylates S6K at Thr-389. S6K also undergoes phosphorylation at other sites, including four serine residues in the autoinhibitory domain. Despite extensive biochemical studies, the importance of phosphorylation in the autoinhibitory domain in S6K function remains unresolved, and its role has not been explored in the cellular context. Here we demonstrated that S6K in neuron was phosphorylated at Ser-411 within the autoinhibitory domain by cyclin-dependent kinase 5. Ser-411 phosphorylation was regulated by neuronal activity and brain-derived neurotrophic factor (BDNF). Knockdown of S6K in hippocampal neurons by RNAi led to loss of dendritic spines, an effect that mimics neuronal activity blockade by tetrodotoxin. Notably, coexpression of wild type S6K, but not the phospho-deficient S411A mutant, could rescue the spine defects. These findings reveal the importance of cyclin-dependent kinase 5-mediated phosphorylation of S6K at Ser-411 in spine morphogenesis driven by BDNF and neuronal activity.-
dc.languageeng-
dc.publisherThe American Society for Biochemistry and Molecular Biology,. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistry-
dc.rightsThis research was originally published in the Journal of Biological Chemistry. Kwok-On Lai, Zhuoyi Liang, Erkang Fei, Huiqian Huang and Nancy Y. Ip. Cyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis. J Biol Chem. 2015; 290:14637-14646. © the American Society for Biochemistry and Molecular Biology.-
dc.titleCyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis-
dc.typeArticle-
dc.identifier.emailLai, KO: laiko@hku.hk-
dc.identifier.authorityLai, KO=rp01891-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1074/jbc.M114.627117-
dc.identifier.pmid25903132-
dc.identifier.pmcidPMC4505530-
dc.identifier.scopuseid_2-s2.0-84930623488-
dc.identifier.hkuros249416-
dc.identifier.volume290-
dc.identifier.issue23-
dc.identifier.spage14637-
dc.identifier.epage14646-
dc.identifier.isiWOS:000355754600034-
dc.identifier.issnl0021-9258-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats