Moe1, a conserved protein in Schizosaccharomyces pombe, interacts with a Ras effector, Scd1, to affect proper spindle formation

Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):517-22. doi: 10.1073/pnas.96.2.517.

Abstract

In fission yeast, Scd1/Ral1 is a putative guanine nucleotide exchange factor for Cdc42sp and also acts as a Ras1 effector necessary for the regulation of cytoskeleton organization. In this study, we have characterized a protein, Moe1, that binds directly to Scd1. A moe1 null (Delta) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Delta mutants are resistant to microtubule destabilizing agents; moreover, moe1Delta rescued the growth defects of tubulin mutants containing unstable microtubules. These results suggest that Moe1 induces instability in microtubules. Biochemical and subcellular localization studies suggest that Moe1 and Scd1 colocalize in the nucleus. Furthermore, loss of function in Scd1 or Ras1 also induced abnormality in the spindle and is synthetically lethal with moe1Delta producing cells that lack a detectable spindle. These data demonstrate that Moe1 is a component of the Ras1 pathway necessary for proper spindle formation in the nucleus. Human and nematode Moe1 both can substitute for yeast Moe1, indicating that the function of Moe1 in spindle formation has been conserved substantially during evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / genetics
  • Cloning, Molecular
  • Eukaryotic Initiation Factors*
  • Evolution, Molecular
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Green Fluorescent Proteins
  • Guanine Nucleotide Exchange Factors*
  • Humans
  • Luminescent Proteins / genetics
  • Microscopy, Fluorescence
  • Microtubules / genetics
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Binding / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins*
  • Sequence Analysis, DNA
  • Spindle Apparatus / metabolism*
  • Tubulin / genetics
  • ras Proteins / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Eukaryotic Initiation Factors
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Luminescent Proteins
  • Moe1 protein, S pombe
  • Proto-Oncogene Proteins
  • Schizosaccharomyces pombe Proteins
  • Tubulin
  • scd1 protein, S pombe
  • Green Fluorescent Proteins
  • ras Proteins

Associated data

  • GENBANK/AF038568