title: Neurabin-I is phosphorylated by Cdk5: implications for neuronal morphogenesis and cortical migration.
abstract: The correct morphology and migration of neurons, which is essential for the normal development of the nervous system, is enabled by the regulation of their cytoskeletal elements. We reveal that Neurabin-I, a neuronal-specific F-actin-binding protein, has an essential function in the developing forebrain. We show that gain and loss of Neurabin-I expression affect neuronal morphology, neurite outgrowth, and radial migration of differentiating cortical and hippocampal neurons, suggesting that tight regulation of Neurabin-I function is required for normal forebrain development. Importantly, loss of Neurabin-I prevents pyramidal neurons from migrating into the cerebral cortex, indicating its essential role during early stages of corticogenesis. We demonstrate that in neurons Rac1 activation is affected by the expression levels of Neurabin-I. Furthermore, the Cdk5 kinase, a key regulator of neuronal migration and morphology, directly phosphorylates Neurabin-I and controls its association with F-actin. Mutation of the Cdk5 phosphorylation site reduces the phenotypic consequences of Neurabin-I overexpression both in vitro and in vivo, suggesting that Neurabin-I function depends, at least in part, on its phosphorylation status. Together our findings provide new insight into the signaling pathways responsible for controlled changes of the F-actin cytoskeleton that are required for normal development of the forebrain.
authors: Department of Cellular and Molecular Neuroscience, Imperial College School of Medicine, Charing Cross Campus, London W6 8RP, United Kingdom.
authors: Frédéric
authors: F
authors: Causeret
authors: Tom
authors: T
authors: Jacobs
authors: Mami
authors: M
authors: Terao
authors: Owen
authors: O
authors: Heath
authors: Mikio
authors: M
authors: Hoshino
authors: Margareta
authors: M
authors: Nikolic
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D002478:Cells, Cultured; D002522:Chlorocebus aethiops / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099273:Neurabins
chemical_list: D000199:Actins; D051360:Cyclin-Dependent Kinase 5; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D020830:rac1 GTP-Binding Protein; D000099273:Neurabins
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