Posterior neocortex-specific regulation of neuronal migration by CEP85L identifies maternal centriole-dependent activation of CDK5
| Autor: | Alicia B. Byrne, Laura Isacco, R. Sean Hill, Wojciech Wiszniewski, Kristin W. Barañano, A. James Barkovich, Anne O’Donnell, David G. Vossler, Julie S. Cohen, Christopher A. Walsh, Kirsty McWalter, Edward Stronge, Christopher J. Yuskaitis, Andrew Kodani, Mustafa Sahin, Dilenny M. Gonzalez, Gabrielle M. Sejourne, Edward Yang, Pawel Gawlinski, Jennifer N. Partlow, S. Ali Fatemi, Abbe Lai, Connor J. Kenny |
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| Přispěvatelé: | Kodani, Andrew, Kenny, Connor, Lai, Abbe, Gonzalez, Dilenny M, Byrne, Alicia B, Walsh, Christopher A |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncogene Proteins Fusion Centriole Cell Lissencephaly Neocortex Nerve Tissue Proteins Microtubules Article Young Adult 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans pachygyria genetics Child Centrioles Neurons biology neurodevelopment General Neuroscience Cyclin-dependent kinase 5 Cyclin-Dependent Kinase 5 Microtubule cytoskeleton organization medicine.disease Cell biology Cytoskeletal Proteins 030104 developmental biology Tubulin medicine.anatomical_structure centrosome LCDK5 nervous system Centrosome Child Preschool biology.protein Female De novo CEP85 030217 neurology & neurosurgery lissencephaly |
| Zdroj: | Neuron |
| Popis: | Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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