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Article: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease

TitleCdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease
Authors
KeywordsChemicals And Cas Registry Numbers: 2-Acylglycerophosphate Acyltransferase, 2.3.1.52
Acyltransferases, 2.3.-
Cdk5 Protein, Mouse, 2.7.1.37
Cyclin-Dependent Kinase 5, 2.7.11.22
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology
Citation
Nature Cell Biology, 2011, v. 13 n. 5, p. 568-579 How to Cite?
AbstractCyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is increasingly implicated in various neurodegenerative diseases. Deregulated Cdk5 activity has been associated with neuronal death, but the underlying mechanisms are not well understood. Here we report an unexpected role for Cdk5 in the regulation of induced autophagy in neurons. We have identified endophilin B1 (EndoB1) as a Cdk5 substrate, and show that Cdk5-mediated phosphorylation of EndoB1 is required for autophagy induction in starved neurons. Furthermore, phosphorylation of EndoB1 facilitates EndoB1 dimerization and recruitment of UVRAG (UV radiation resistance-associated gene). More importantly, Cdk5-mediated phosphorylation of EndoB1 is essential for autophagy induction and neuronal loss in models of Parkinson's disease. Our findings not only establish Cdk5 as a critical regulator of autophagy induction, but also reveal a role for Cdk5 and EndoB1 in the pathophysiology of Parkinson's disease through modulating autophagy. © 2011 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/145836
ISSN
2015 Impact Factor: 18.699
2015 SCImago Journal Rankings: 14.131
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong (HKUST)661007
661109
660309
660210
1/06C
6/CRF/08
University Grants CommitteeAoE/B-15/01
Hong Kong Jockey Club
Croucher Foundation
Funding Information:

We are grateful to A. B. Kulkarni (National Institutes of Health, USA) and T. Curran (St Jude Children's Research Hospital, USA) for the Cdk5-knockout mice. p35-knockout mice were provided by L. H. Tsai (Massachusetts Institute of Technology, USA). We thank T. Yoshimori (Osaka University, Japan) for the mRFP-LC3 construct, V.M.Y. Lee (University of Pennsylvania School of Medicine, USA) for the SNL-1 antibody and wild-type alpha synuclein and alpha-synucleinA53T constructs and J. Yuan (Harvard Medical School) for the pcDNA3-Beclin 1 construct. We thank J. Li, G. Ke, W.Y. Fu, K. Cheng, J. Wan, Y.P. Ng, V. Lee and A. Lai for technical assistance, and members of the Ip lab oratory for discussions. This work was supported in part by the Research Grants Council of Hong Kong (HKUST 661007, 661109, 660309, 660210, 1/06C and 6/CRF/08), the Area of Excellence Scheme of the University Grants Committee (AoE/B-15/01) and the Hong Kong Jockey Club. N.Y.I. and Z.H.C. were recipients of the Croucher Foundation Senior Research Fellowship and Croucher Foundation Fellowship, respectively.

References
Errata

 

DC FieldValueLanguage
dc.contributor.authorWong, ASLen_HK
dc.contributor.authorLee, RHKen_HK
dc.contributor.authorCheung, AYen_HK
dc.contributor.authorYeung, PKen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorCheung, ZHen_HK
dc.contributor.authorIp, NYen_HK
dc.date.accessioned2012-03-23T09:49:55Z-
dc.date.available2012-03-23T09:49:55Z-
dc.date.issued2011en_HK
dc.identifier.citationNature Cell Biology, 2011, v. 13 n. 5, p. 568-579en_HK
dc.identifier.issn1465-7392en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145836-
dc.description.abstractCyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is increasingly implicated in various neurodegenerative diseases. Deregulated Cdk5 activity has been associated with neuronal death, but the underlying mechanisms are not well understood. Here we report an unexpected role for Cdk5 in the regulation of induced autophagy in neurons. We have identified endophilin B1 (EndoB1) as a Cdk5 substrate, and show that Cdk5-mediated phosphorylation of EndoB1 is required for autophagy induction in starved neurons. Furthermore, phosphorylation of EndoB1 facilitates EndoB1 dimerization and recruitment of UVRAG (UV radiation resistance-associated gene). More importantly, Cdk5-mediated phosphorylation of EndoB1 is essential for autophagy induction and neuronal loss in models of Parkinson's disease. Our findings not only establish Cdk5 as a critical regulator of autophagy induction, but also reveal a role for Cdk5 and EndoB1 in the pathophysiology of Parkinson's disease through modulating autophagy. © 2011 Macmillan Publishers Limited. All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiologyen_HK
dc.relation.ispartofNature Cell Biologyen_HK
dc.subjectChemicals And Cas Registry Numbers: 2-Acylglycerophosphate Acyltransferase, 2.3.1.52en_US
dc.subjectAcyltransferases, 2.3.-en_US
dc.subjectCdk5 Protein, Mouse, 2.7.1.37en_US
dc.subjectCyclin-Dependent Kinase 5, 2.7.11.22en_US
dc.subject.meshAcyltransferases - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAutophagyen_HK
dc.subject.meshCyclin-Dependent Kinase 5 - chemistry - metabolismen_HK
dc.subject.meshDisease Models, Animalen_HK
dc.subject.meshMiceen_HK
dc.subject.meshParkinson Disease - metabolism - pathologyen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProtein Bindingen_HK
dc.titleCdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.emailChung, SK:skchung@hkucc.hku.hken_HK
dc.identifier.emailCheung, ZH:zelda@hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityCheung, ZH=rp01588en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ncb2217en_HK
dc.identifier.pmid21499257-
dc.identifier.scopuseid_2-s2.0-79955589665en_HK
dc.identifier.hkuros189419-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955589665&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume13en_HK
dc.identifier.issue5en_HK
dc.identifier.spage568en_HK
dc.identifier.epage579en_HK
dc.identifier.eissn1476-4679-
dc.identifier.isiWOS:000290148700016-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.erratumdoi:10.1038/ncb0611-734d-
dc.identifier.scopusauthoridWong, ASL=37102817200en_HK
dc.identifier.scopusauthoridLee, RHK=37102028400en_HK
dc.identifier.scopusauthoridCheung, AY=25421547900en_HK
dc.identifier.scopusauthoridYeung, PK=35486097200en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridCheung, ZH=6507483375en_HK
dc.identifier.scopusauthoridIp, NY=7005756760en_HK
dc.identifier.citeulike9236549-

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