Nuclear envelope bridging proteins function in nuclear positioning and cell cycle progression.

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Nuclear envelope KASH (Klarsicht, ANC-1, Syne Homology) and SUN (Sad1p, UNC-84) proteins localize to the outer and inner nuclear membranes, respectively. They function in nuclear positioning, meiotic homolog pairing, and maintenance of nuclear architecture. A novel mechanism to retain KASH proteins at the outer nuclear membrane through a direct interaction with the SUN proteins UNC-84 and SUN-1 was described. A KASH domain in the Caenorhabditis elegans nuclear positioning protein UNC-83 was identified and found to be necessary for localization and function. UNC-83 localization and function were partially rescued by an UNC-83 chimeric protein with the Homo sapiens Nesprin-3 KASH domain. Point mutations in the UNC-83 KASH domain partially disrupted function, but not localization. This suggested a strong force required for nuclear positioning and a weaker one for retention at the outer nuclear membrane. The SUN domain of Caenorhabditis elegans UNC-84 was required for its function in vivo, but not its localization. I proposed a model in which KASH and SUN proteins interact in the perinuclear space to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoskeleton. An unstudied Caenorhabditis elegans KASH protein KDP-1 (KASH Domain Protein) was identified in a membrane-bound yeast two-hybrid (MYTH) screen for UNC-84-interacting proteins. KDP-1 also interacted with the Caenorhabditis elegans SUN protein SUN-1. KDP-1 had a divergent KASH domain. KDP-1 localized to the nuclear envelope of germline nuclei in a sun-1-dependent manner and partially phenocopied sun-1 germline defects. KDP-1 also localized to somatic tissues, often at the nuclear envelope. These data suggested that KDP-1 is a KASH protein. kdp-1(RNAi) gonads had a small mitotic zone and endomitotic oocytes in the proximal germline. kdp-1 was required for embryonic viability, with defects in cell cycle progression in the germline and early embryo. kdp-1 was also required for larval growth and nuclear envelope integrity. This supported a model in which KDP-1 is a KASH protein required for timely progression from S phase to mitosis, a function not previously attributed to KASH proteins.
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Product Details

  • BN ID: 2940032605195
  • Publisher: ProQuest LLC
  • Sold by: Barnes & Noble
  • Format: eTextbook
  • Pages: 128

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