A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import.
Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE. We report a novel role for torsin in nuclear pore biology. In ooc-5-mutant germ cell nuclei, nucleoporins (Nups) were mislocalized in large plaques beginning at meiotic entry and persisted throughout meiosis. Moreover, the KASH protein ZYG-12 was mislocalized in ooc-5 gonads. Nups were mislocalized in adult intestinal nuclei and in embryos from mutant mothers. EM analysis revealed vesicle-like structures in the perinuclear space of intestinal and germ cell nuclei, similar to defects reported in torsin-mutant flies and mice. Consistent with a functional disruption of Nups, ooc-5-mutant embryos displayed impaired nuclear import kinetics, although the nuclear pore-size exclusion barrier was maintained. Our data are the first to demonstrate a requirement for a torsin for normal Nup localization and function and suggest that these functions are likely conserved.
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616 mjwvangompel@ucdavis.edu lsrose@ucdavis.edu.
Michael J W
MJ
VanGompel
Center for C. elegans Anatomy, Albert Einstein College of Medicine, New York, NY 10461.
Ken C Q
KC
Nguyen
Center for C. elegans Anatomy, Albert Einstein College of Medicine, New York, NY 10461.
David H
DH
Hall
Departments of Neurology and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109.
William T
WT
Dauer
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616 mjwvangompel@ucdavis.edu lsrose@ucdavis.edu.
Lesilee S
LS
Rose
D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005854:Germ Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D009685:Nuclear Envelope / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D028861:Nuclear Pore Complex Proteins; C480800:zyg-12 protein, C elegans; D000251:Adenosine Triphosphatases; C442329:OOC-5 protein, C elegans