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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, 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

 

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, p. 14637-14646-
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.rightsCreative Commons: Attribution 3.0 Hong Kong License-
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.hkuros249416-
dc.identifier.volume290-
dc.identifier.spage14637-
dc.identifier.epage14646-

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