title: Phosphorylation of Connexin 43 by Cdk5 Modulates Neuronal Migration During Embryonic Brain Development.
abstract: The gap junction protein, connexin 43 (Cx43), is only present and abundantly expressed in astrocytes but is absent in neurons in the mature brain tissues. However, both the expression and function of Cx43 in neurons during brain embryonic development remain largely unexplored. In the present study, we confirmed that Cx43 is expressed in the migrating neurons in the embryonic stage of the brain. Neuron-specific Cx43 conditional knockout (cKO) using Cre-loxP technique impairs neuronal migration and formation of laminar structure in cerebral cortex during brain embryonic development. The animal behavior tests demonstrated that, at the adult stage, neuronal Cx43 cKO mice exhibit normal learning and memory functions but increased anxiety-like behavior. We also found that during the embryonic development, the gradually decreased Cx43 expression in the cortex is closely correlated with the upregulation of cyclin-dependent kinase 5 (Cdk5) activity. Cdk5 directly phosphorylates Cx43 at Ser279 and Ser282, which, in consequence, inhibits the membrane targeting of Cx43 and promotes its proteasome-dependent degradation. In summary, our findings revealed that the embryonic expression of Cx43 in neurons regulates processes of neuronal migration and positioning in the developing brain by controlling astrocyte-neuron interactions during brain embryonic development, and Cdk5 directly phosphorylates Cx43, which regulates the membrane localization and degradation of Cx43 in neurons.
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Qi
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Bu
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Shao
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Jiao
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. tianbo@mails.tjmu.edu.cn.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. tianbo@mails.tjmu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Tian
mesh_terms: D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D018031:Connexin 43 / Q000737:chemistry / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008568:Memory; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009928:Organ Specificity; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis
chemical_list: D018031:Connexin 43; D010768:Phosphoserine; D051360:Cyclin-Dependent Kinase 5; D046988:Proteasome Endopeptidase Complex
keywords: Connexin 43; Cyclin-dependent kinase 5; Neuronal development; Neuronal migration; Protein phosphorylation