Abstract
ABSTRACTThe 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, we show here that when scd1 function is compromised, disruption of microtubules or the polarity landmark proteins Tea1, Tea4 or Pom1 leads to disruption of polarized growth. Instead, cells adopt an isotropic-like pattern of growth, which we term PORTLI growth. Surprisingly, PORTLI growth is caused by spatially inappropriate activity of Gef1. Although most Cdc42 GEFs are membrane associated, we find that Gef1 is a broadly distributed 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 suggest a new model of fission yeast cell polarity regulation, involving coordination of ‘local’ (Scd1) and ‘global’ (Gef1) Cdc42 GEFs via microtubules and microtubule-dependent polarity landmarks.
Highlights
Cell polarity is essential for many eukaryotic cell functions, including migration and/or directional growth, intracellular transport, cell signaling, asymmetric cell division and tissue organization (Campanale et al, 2017; Mayor and Etienne-Manneville, 2016; Rodriguez-Boulan and Macara, 2014; Schelski and Bradke, 2017; St Johnston and Ahringer, 2010)
Our results reveal a previously unrecognized role for MTs and the Tea1–Tea4–Pom1 axis in the maintenance of fission yeast cell polarity, and they suggest a model in which local and global Cdc42 guanine nucleotide exchange factors (GEFs) are active in parallel but regulated by different mechanisms
Cell polarity regulation by local and global Cdc42 GEFs Our results suggest a conceptual model for Cdc42- and MTmediated cell polarity regulation in fission yeast (Fig. 8) that is significantly different from previous models (Chang and Martin, 2009; Hachet et al, 2012; Rincón et al, 2014; Sawin and Snaith, 2004; Chiou et al, 2017; Kokkoris et al, 2014; Martin and Arkowitz, 2014)
Summary
Cell polarity is essential for many eukaryotic cell functions, including migration and/or directional growth, intracellular transport, cell signaling, asymmetric cell division and tissue organization (Campanale et al, 2017; Mayor and Etienne-Manneville, 2016; Rodriguez-Boulan and Macara, 2014; Schelski and Bradke, 2017; St Johnston and Ahringer, 2010). Control of Cdc activity by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs) is a crucial feature of polarity regulation (Bos et al, 2007; Cook et al, 2014; Hodge and Ridley, 2016; Moon and Zheng, 2003; Rossman et al, 2005)
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