| Nuclear positioning is essential for formation of polarized cells, pronuclear migration, cell division, cell migration, cell differentiation and the formation of syncytial structures. Defects in nuclear positioning events have been linked to a number of human diseases. Many mechanisms of nuclear migration in various systems involve microtubules and microtubule motors. Microtubule-based mechanisms of nuclear positioning can be classified as centrosome-dependent and centrosome-independent. The former requires tight association of the microtubule organizing center (MTOC) with the nuclear envelope, while the latter resembles cytoplasmic trafficking of cargo by microtubule motors. Here I describe mechanisms for two nuclear migration events in the nematode Caenorhabditis elegans. The first affects pronuclear migration and requires centrosome attachment to the envelope of the male pronucleus. The second occurs in the pre-elongation stage of embryonic development and is centrosome-independent. Both events utilize members of the SUN and KASH protein families, which form a bridge across the nuclear envelope.;In C. elegans zygotes, small pronuclei and a single centrosome detachment phenotype were observed upon simultaneous depletion of nuclear lamina proteins or nuclear import components. Time-lapse images showed that as mutant pronuclei grew in surface area, they captured detached centrosomes. Enlargement or reduction of nuclei using genetic tools suppressed or enhanced the centrosome detachment phenotype, respectively. These data suggest a model in which dynein on the surface of small pronuclei is sufficient for interaction with microtubules from one centrosome only.;Several nuclear migration events in the C.elegans embryo and early larva require the KASH domain protein UNC-83, which functions with the SUN domain protein UNC-84 to bridge the nuclear envelope. The kinesin-1 light chain, KLC-2, was identified as a binding partner of UNC-83 by several in vitro assays. Kinesin-1 mutants displayed defects in the nuclear migration. UNC-83 was shown to recruit KLC-2 to the nuclear envelope in a heterologous tissue culture system. Finally, expression of a KLC-2::KASH fusion protein partially bypassed the requirement for UNC-83 in nuclear migration. These data lead to a model in which UNC-83 acts as a kinesin-1 cargo-specific adapter, allowing motor-generated forces to be transferred from the cytoplasm to the nuclear lamina. |
