Fission yeast Ras1 effector Scd1 interacts with the spindle and affects its proper formation

Genetics. 2000 Nov;156(3):995-1004.

Abstract

Ras1 GTPase is the Schizosaccharomyces pombe homolog of the mammalian Ha-Ras proto-oncoprotein. Ras1 interacts with Scd1 (aka Ral1), a presumptive guanine nucleotide exchange factor for Cdc42sp, to control organization of the cytoskeleton. In this study, we demonstrated that the scd1 deletion (scd1Delta) induced hypersensitivity to microtubule destabilizing drugs and instability of the minichromosome. Overexpression of scd1 induced formation of abnormal spindles and chromosome missegregation. The scd1 deletion worsened the defects of spindle formation in tubulin mutants; by contrast, it did not induce lethality in mutants defective in the spindle pole bodies. These genetic data suggest that Scd1 can interact with tubulin with substantial specificity to affect proper spindle formation and chromosome segregation. Subcellular localization data further illustrated that a GFP-Scd1 fusion protein can associate with the spindle. Finally, we showed that unlike ras1Delta and scd1Delta, byr2Delta (affecting the Ras1 effector for mating) is not synthetically lethal with the tubulin mutations. These data collectively suggest that the Ras1 pathway can impinge upon microtubules through Scd1, but not Byr2, to affect proper spindle formation and chromosome segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Chromosomes, Fungal / genetics
  • Cytoskeleton / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Deletion
  • Guanine Nucleotide Exchange Factors*
  • Mammals
  • Mutagenesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins*
  • Spindle Apparatus / genetics
  • Thiamine / pharmacology
  • Tubulin / genetics
  • ras GTPase-Activating Proteins / genetics

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Proto-Oncogene Proteins
  • Schizosaccharomyces pombe Proteins
  • Tubulin
  • ras GTPase-Activating Proteins
  • scd1 protein, S pombe
  • Thiamine