title: TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement.
abstract: The nucleus is positioned toward the rear of most migratory cells. In fibroblasts and myoblasts polarizing for migration, retrograde actin flow moves the nucleus rearward, resulting in the orientation of the centrosome in the direction of migration. In this study, we report that the nuclear envelope-localized AAA+ (ATPase associated with various cellular activities) torsinA (TA) and its activator, the inner nuclear membrane protein lamina-associated polypeptide 1 (LAP1), are required for rearward nuclear movement during centrosome orientation in migrating fibroblasts. Both TA and LAP1 contributed to the assembly of transmembrane actin-associated nuclear (TAN) lines, which couple the nucleus to dorsal perinuclear actin cables undergoing retrograde flow. In addition, TA localized to TAN lines and was necessary for the proper mobility of EGFP-mini-nesprin-2G, a functional TAN line reporter construct, within the nuclear envelope. Furthermore, TA and LAP1 were indispensable for the retrograde flow of dorsal perinuclear actin cables, supporting the recently proposed function for the nucleus in spatially organizing actin flow and cytoplasmic polarity. Collectively, these results identify TA as a key regulator of actin-dependent rearward nuclear movement during centrosome orientation.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Cosmo A
authors.initials: CA
authors.lastname: Saunders
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Harris
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Willey
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Woolums
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032.|Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McQuown
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Amy
authors.initials: A
authors.lastname: Schoenhofen
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032.|Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Howard J
authors.identifier: 0000-0002-7063-7889
authors.initials: HJ
authors.lastname: Worman
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.|Department of Neurology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: William T
authors.initials: WT
authors.lastname: Dauer
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 gwgl@umn.edu ggg1@columbia.edu.
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 gwgl@umn.edu ggg1@columbia.edu.
authors.forename: G W Gant
authors.identifier: 0000-0002-6180-8906
authors.initials: GW
authors.lastname: Luxton
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C491548:Dyt1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins