title: Depletion of kinesin-12, a myosin-IIB-interacting protein, promotes migration of cortical astrocytes.
abstract: Kinesin-12 (also named Kif15) participates in important events during neuronal development, such as cell division of neuronal precursors, migration of young neurons and establishment of axons and dendritic arbors, by regulating microtubule organization. Little is known about the molecular mechanisms behind the functions of kinesin-12, and even less is known about its roles in other cell types of the nervous system. Here, we show that kinesin-12 depletion from cultured rat cortical astrocytes decreases cell proliferation but increases migration. Co-immunoprecipitation, GST pulldown and small interfering RNA (siRNA) experiments indicated that kinesin-12 directly interacts with myosin-IIB through their tail domains. Immunofluorescence analyses indicated that kinesin-12 and myosin-IIB colocalize in the lamellar region of astrocytes, and fluorescence resonance energy transfer analyses revealed an interaction between the two. The phosphorylation at Thr1142 of kinesin-12 was vital for their interaction. Loss of their interaction through expression of a phosphorylation mutant of kinesin-12 promoted astrocyte migration. We suggest that kinesin-12 and myosin-IIB can form a hetero-oligomer that generates force to integrate microtubules and actin filaments in certain regions of cells, and in the case of astrocytes, that this interaction can modulate their migration.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Zunlu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Haijiao
authors.identifier: 0000-0002-9615-8691
authors.initials: H
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hua
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Zhangji
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China.
authors.forename: Yan
authors.identifier: 0000-0003-1168-6119
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong Jiangsu 226001, China liumei@ntu.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D031541:Fluorescence Resonance Energy Transfer; D016547:Kinesins / Q000378:metabolism*; D008954:Models, Biological; D024501:Nonmuscle Myosin Type IIB / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D000072417:Protein Domains; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000166:cytology
chemical_list: C481488:Kif15 protein, rat; D034741:RNA, Small Interfering; D024501:Nonmuscle Myosin Type IIB; D016547:Kinesins
keywords: Kif15; Kinesin-12; Microtubule; Migration; Myosin-IIB; Protein interaction; Rat astrocytes