title: toca-1 is in a novel pathway that functions in parallel with a SUN-KASH nuclear envelope bridge to move nuclei in Caenorhabditis elegans.
abstract: Moving the nucleus to an intracellular location is critical to many fundamental cell and developmental processes, including cell migration, differentiation, fertilization, and establishment of cellular polarity. Bridges of SUN and KASH proteins span the nuclear envelope and mediate many nuclear positioning events, but other pathways function independently through poorly characterized mechanisms. To identify and characterize novel mechanisms of nuclear migration, we conducted a nonbiased forward genetic screen for mutations that enhanced the nuclear migration defect of unc-84, which encodes a SUN protein. In Caenorhabditis elegans larvae, failure of hypodermal P-cell nuclear migration results in uncoordinated and egg-laying-defective animals. The process of P-cell nuclear migration in unc-84 null animals is temperature sensitive; at 25° migration fails in unc-84 mutants, but at 15° the migration occurs normally. We hypothesized that an additional pathway functions in parallel to the unc-84 pathway to move P-cell nuclei at 15°. In support of our hypothesis, forward genetic screens isolated eight emu (enhancer of the nuclear migration defect of unc-84) mutations that disrupt nuclear migration only in a null unc-84 background. The yc20 mutant was determined to carry a mutation in the toca-1 gene. TOCA-1 functions to move P-cell nuclei in a cell-autonomous manner. TOCA-1 is conserved in humans, where it functions to nucleate and organize actin during endocytosis. Therefore, we have uncovered a player in a previously unknown, likely actin-dependent, pathway that functions to move nuclei in parallel to SUN-KASH bridges. The other emu mutations potentially represent other components of this novel pathway.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Yu-Tai
authors.initials: YT
authors.lastname: Chang
authors.forename: Daniel
authors.initials: D
authors.lastname: Dranow
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kuhn
authors.forename: Marina
authors.initials: M
authors.lastname: Meyerzon
authors.forename: Minh
authors.initials: M
authors.lastname: Ngo
authors.forename: Dmitry
authors.initials: D
authors.lastname: Ratner
authors.forename: Karin
authors.initials: K
authors.lastname: Warltier
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Starr
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002874:Chromosome Mapping; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D021381:Protein Transport; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C544270:KDP-1 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C545960:TOCA-1 protein, C elegans; C120560:Unc-84 protein, C elegans