Local and global Cdc42 GEFs for fission yeast cell polarity are coordinated by microtubules and the Tea1/Tea4/Pom1 axis

Abstract

The conserved Rho-family GTPase Cdc42 plays a central role in eukaryotic cell polarity. The rod-shaped fission yeast Schizosaccharomyces pombe has two Cdc42 guanine-nucleotide exchange factors (GEFs), Scd1 and Gef1, but little is known about how they are coordinated in polarized growth. Although the microtubule cytoskeleton is normally not required for polarity maintenance in fission yeast, here we show that when scdl function is compromised, disruption of microtubules or the polarity landmark proteins Tea1, Tea4, or Pom1 leads to isotropic rather than polarized growth. Surprisingly, this isotropic growth is due to spatially inappropriate activity of Gef1, which is a cytosolic protein rather than a membrane-associated protein at cell tips like Scd1. Microtubules and the Tea1/Tea4/Pom1 axis counteract inappropriate Gef1 activity by regulating the localization of the Cdc42 GTPase-activating protein Rga4. Our results thus demonstrate coordination of \"local\" (Scd1) and \"global\" (Gef1) Cdc42 GEFs via microtubules and microtubule-dependent polarity landmarks.