4.5 Article

KDP-1 is a nuclear envelope KASH protein required for cell-cycle progression

Journal

JOURNAL OF CELL SCIENCE
Volume 122, Issue 16, Pages 2895-2905

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.051607

Keywords

KASH protein; Outer nuclear membrane; Nuclear envelope; Cell cycle; SUN protein; C. elegans

Categories

Funding

  1. Canadian Foundation for Innovation (CFI)
  2. Canadian Institute for Health Research (CIHR)
  3. Canadian Cancer Society
  4. Heart and Stroke Foundation of Canada
  5. Novartis
  6. National Institutes of Health [R01GM073874]

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Klarsicht, ANC-1 and Syne homology (KASH) proteins localize to the outer nuclear membrane where they connect the nucleus to the cytoskeleton. KASH proteins interact with Sad1-UNC-84 (SUN) proteins to transfer forces across the nuclear envelope to position nuclei or move chromosomes. A new KASH protein, KDP-1, was identified in a membrane yeast two-hybrid screen of a Caenorhabditis elegans library using the SUN protein UNC-84 as bait. KDP-1 also interacted with SUN-1. KDP-1 was enriched at the nuclear envelope in a variety of tissues and required SUN-1 for nuclear envelope localization in the germline. Genetic analyses showed that kdp-1 was essential for embryonic viability, larval growth and germline development. kdp-1(RNAi) delayed the entry into mitosis in embryos, led to a small mitotic zone in the germline, and caused an endomitotic phenotype. Aspects of these phenotypes were similar to those seen in sun-1(RNAi), suggesting that KDP-1 functions with SUN-1 in the germline and early embryo. The data suggest that KDP-1 is a novel KASH protein that functions to ensure the timely progression of the cell cycle between the end of S phase and the entry into mitosis.

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