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

In fission yeast, Scd1/Ra11 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 nu11 (Δ) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Δ mutants are resistant to microtubule destabilizing agents; moreover, moe1δ 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 moe1Δ 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.