Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
| العنوان: | Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex |
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| المؤلفون: | Amy K.Y. Fu, Tao Ye, Jacque P.K. Ip, Nancy Y. Ip |
| المصدر: | Nature Communications |
| بيانات النشر: | Nature Pub. Group, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | General Physics and Astronomy, Fluorescent Antibody Technique, Nerve Tissue Proteins, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, Downregulation and upregulation, Cell Movement, medicine, Guanine Nucleotide Exchange Factors, Humans, Phosphorylation, RNA, Small Interfering, Cerebral Cortex, Neurons, Multidisciplinary, Chemistry, Kinase, RAPGEF2, Cyclin-dependent kinase 5, Gene Expression Regulation, Developmental, Cyclin-Dependent Kinase 5, General Chemistry, Immunohistochemistry, Cell biology, medicine.anatomical_structure, Electroporation, nervous system, Cerebral cortex, Rap1, Guanine nucleotide exchange factor |
| الوصف: | During cerebral cortex development, pyramidal neurons migrate through the intermediate zone and integrate into the cortical plate. These neurons undergo the multipolar–bipolar transition to initiate radial migration. While perturbation of this polarity acquisition leads to cortical malformations, how this process is initiated and regulated is largely unknown. Here we report that the specific upregulation of the Rap1 guanine nucleotide exchange factor, RapGEF2, in migrating neurons corresponds to the timing of this polarity transition. In utero electroporation and live-imaging studies reveal that RapGEF2 acts on the multipolar–bipolar transition during neuronal migration via a Rap1/N-cadherin pathway. Importantly, activation of RapGEF2 is controlled via phosphorylation by a serine/threonine kinase Cdk5, whose activity is largely restricted to the radial migration zone. Thus, the specific expression and Cdk5-dependent phosphorylation of RapGEF2 during multipolar–bipolar transition within the intermediate zone are essential for proper neuronal migration and wiring of the cerebral cortex. During cerebral cortex development, pyramidal neurons migrate and integrate into the cortical plate after undergoing a multipolar–bipolar transition to initiate radial migration. Here the authors show that the downstream target of Cdk5, RapGEF2, is critical for this polarity transition and the migration and integration of neurons into the cortex. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57e788fc35651a1125c918e03a7b6a03Test http://europepmc.org/articles/PMC4164783Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....57e788fc35651a1125c918e03a7b6a03 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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