UNC-83 is a nuclear-specific cargo adaptor for kinesin-1-mediated nuclear migration

Development. 2009 Aug;136(16):2725-33. doi: 10.1242/dev.038596. Epub 2009 Jul 15.

Abstract

Intracellular nuclear migration is essential for many cellular events including fertilization, establishment of polarity, division and differentiation. How nuclei migrate is not understood at the molecular level. The C. elegans KASH protein UNC-83 is required for nuclear migration and localizes to the outer nuclear membrane. UNC-83 interacts with the inner nuclear membrane SUN protein UNC-84 and is proposed to connect the cytoskeleton to the nuclear lamina. Here, we show that UNC-83 also interacts with the kinesin-1 light chain KLC-2, as identified in a yeast two-hybrid screen and confirmed by in vitro assays. UNC-83 interacts with and recruits KLC-2 to the nuclear envelope in a heterologous tissue culture system. Additionally, analysis of mutant phenotypes demonstrated that both KLC-2 and the kinesin-1 heavy chain UNC-116 are required for nuclear migration. Finally, the requirement for UNC-83 in nuclear migration could be partially bypassed by expressing a synthetic outer nuclear membrane KLC-2::KASH fusion protein. Our data support a model in which UNC-83 plays a central role in nuclear migration by acting to bridge the nuclear envelope and as a kinesin-1 cargo-specific adaptor so that motor-generated forces specifically move the nucleus as a single unit.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Cytoskeleton / metabolism
  • HeLa Cells
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • UNC-116 protein, C elegans
  • Unc-83 protein, C elegans
  • Kinesins