PUBLICATION
Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons.
- Authors
- Balastik, M., Zhou, X. Z., Alberich-Jorda, M., Weissova, R., Žiak, J., Pazyra-Murphy, M. F., Cosker, K. E., Machonova, O., Kozmikova, I., Chen, C. H., Pastorino, L., Asara, J. M., Cole, A., Sutherland, C., Segal, R. A., Lu, K.P.
- ID
- ZDB-PUB-160510-13
- Date
- 2015
- Source
- Cell Reports 13(4): 812-28 (Journal)
- Registered Authors
- Machonova, Olga
- Keywords
- none
- MeSH Terms
-
- Animals
- Axons/metabolism*
- Cell Line, Tumor
- Female
- Humans
- Immunohistochemistry
- Immunoprecipitation
- Male
- NIMA-Interacting Peptidylprolyl Isomerase
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Peptidylprolyl Isomerase/genetics
- Peptidylprolyl Isomerase/metabolism*
- Phosphorylation
- Signal Transduction
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 26489457 Full text @ Cell Rep.
Citation
Balastik, M., Zhou, X. Z., Alberich-Jorda, M., Weissova, R., Žiak, J., Pazyra-Murphy, M. F., Cosker, K. E., Machonova, O., Kozmikova, I., Chen, C. H., Pastorino, L., Asara, J. M., Cole, A., Sutherland, C., Segal, R. A., Lu, K.P. (2015) Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons.. Cell Reports. 13(4):812-28.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping