C. elegans nucleostemin is required for larval growth and germline stem cell division

PLoS Genet. 2008 Aug 22;4(8):e1000181. doi: 10.1371/journal.pgen.1000181.

Abstract

The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell-specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogenesis or by another nucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematode C. elegans, which enables us to examine nst-1 function during both proliferation and differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is localized to the nucleolus and the nucleoplasm; however, its expression is found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1) leads to a larval arrest phenotype due to a growth defect in the soma, while loss of nst-1 specifically in the germ line causes germline stem cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not present in regions of the nucleolus where rRNA transcription and processing occurs, so this reduction is likely secondary to a different defect in ribosome biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain for stable expression and both its G1 GTPase and intermediate domains for proper germ line function. Our data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Division*
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism
  • Cell Proliferation
  • Cytoskeletal Proteins
  • Female
  • Larva / cytology
  • Larva / genetics
  • Larva / growth & development*
  • Larva / metabolism
  • Male
  • Mice
  • Mutation
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Spermatozoa / chemistry
  • Spermatozoa / cytology
  • Spermatozoa / metabolism
  • Stem Cells / chemistry
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CEP-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • nst-1 protein, C elegans