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Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons
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SYSNO ASEP 0455250 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons Author(s) Balaštík, Martin (FGU-C) RID, ORCID
Zhou, X.Z. (US)
Alberich-Jorda, M. (US)
Weissová, Romana (FGU-C) ORCID, RID, SAI
Žiak, Jakub (FGU-C) RID, ORCID
Pazyra-Murphy, M.F. (US)
Cosker, K.E. (US)
Machoňová, O. (CZ)
Kozmiková, I. (CZ)
Chen, CH. (US)
Pastorino, L. (US)
Asara, J.M. (US)
Cole, A. (GB)
Sutherland, C. (GB)
Segal, R. A. (US)
Lu, K.P. (US)Source Title Cell Reports. - : Cell Press - ISSN 2211-1247
Roč. 13, č. 4 (2015), s. 812-828Number of pages 17 s. Language eng - English Country US - United States Keywords Pin1 ; axon guidance ; Semaphorin 3A Subject RIV ED - Physiology Institutional support FGU-C - RVO:67985823 UT WOS 000363780900016 EID SCOPUS 84945540482 DOI https://doi.org/10.1016/j.celrep.2015.09.026 Annotation 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 Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2016
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