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Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons
M. Balastik, XZ. Zhou, M. Alberich-Jorda, R. Weissova, J. Žiak, MF. Pazyra-Murphy, KE. Cosker, O. Machonova, I. Kozmikova, CH. Chen, L. Pastorino, JM. Asara, A. Cole, C. Sutherland, RA. Segal, KP. Lu,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
NLK
Cell Press Free Archives
od 2012
Directory of Open Access Journals
od 2012
Free Medical Journals
od 2012
Freely Accessible Science Journals
od 2012-01-26
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-26
- MeSH
- axony metabolismus MeSH
- dánio pruhované MeSH
- fosforylace MeSH
- imunohistochemie MeSH
- imunoprecipitace MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- peptidylprolylisomerasa genetika metabolismus MeSH
- proteiny dánia pruhovaného genetika metabolismus MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Axon guidance relies on precise translation of extracellular signal gradients into local changes in cytoskeletal dynamics, but the molecular mechanisms regulating dose-dependent responses of growth cones are still poorly understood. Here, we show that during embryonic development in growing axons, a low level of Semaphorin3A stimulation is buffered by the prolyl isomerase Pin1. We demonstrate that Pin1 stabilizes CDK5-phosphorylated CRMP2A, the major isoform of CRMP2 in distal axons. Consequently, Pin1 knockdown or knockout reduces CRMP2A levels specifically in distal axons and inhibits axon growth, which can be fully rescued by Pin1 or CRMP2A expression. Moreover, Pin1 knockdown or knockout increases sensitivity to Sema3A-induced growth cone collapse in vitro and in vivo, leading to developmental abnormalities in axon guidance. These results identify an important isoform-specific function and regulation of CRMP2A in controlling axon growth and uncover Pin1-catalyzed prolyl isomerization as a regulatory mechanism in axon guidance.
Biomedical Research Institute University of Dundee Ninewells Hospital Dundee DD1 9SY Scotland UK
Department of Neurobiology Harvard Medical School Boston MA 02115 USA
Department of Pediatric Oncology and Cancer Biology Dana Farber Cancer Institute Boston MA 02215 USA
Institute for Translational Medicine Fujian Medical University Fuzhou 350108 China
Institute of Molecular Genetics Vídeňská 1083 142 20 Prague 4 Czech Republic
Institute of Physiology Vídeňská 1083 142 20 Prague 4 Czech Republic
Citace poskytuje Crossref.org
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