title: UNC-83 coordinates kinesin-1 and dynein activities at the nuclear envelope during nuclear migration.
abstract: Nuclei migrate during many events, including fertilization, establishment of polarity, differentiation, and cell division. The Caenorhabditis elegans KASH protein UNC-83 localizes to the outer nuclear membrane where it recruits kinesin-1 to provide the major motor activity required for nuclear migration in embryonic hyp7 cells. Here we show that UNC-83 also recruits two dynein-regulating complexes to the cytoplasmic face of the nucleus that play a regulatory role. One consists of the NudE homolog NUD-2 and the NudF/Lis1/Pac1 homolog LIS-1, and the other includes dynein light chain DLC-1, the BicaudalD homolog BICD-1, and the Egalitarian homologue EGAL-1. Genetic disruption of any member of these two complexes caused nuclear migration defects that were enhanced in some double mutant animals, suggesting that BICD-1 and EGAL-1 function in parallel to NUD-2. Dynein heavy chain mutant animals also had a nuclear migration defect, suggesting these complexes function through dynein. Deletion analysis indicated that independent domains of UNC-83 interact with kinesin and dynein. These data suggest a model where UNC-83 acts as the cargo-specific adaptor between the outer nuclear membrane and the microtubule motors kinesin-1 and dynein. Kinesin-1 functions as the major force generator during nuclear migration, while dynein is involved in regulation of bidirectional transport of the nucleus.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Heidi N
authors.initials: HN
authors.lastname: Fridolfsson
authors.forename: Nina
authors.initials: N
authors.lastname: Ly
authors.forename: Marina
authors.initials: M
authors.lastname: Meyerzon
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Starr
mesh_terms: D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C446030:Unc-83 protein, C elegans; C513193:lis-1 protein, C elegans; D004398:Dyneins; D016547:Kinesins