Cell Polarity in Yeast

Abstract

A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

Quantitative analysis of the yeast pheromone pathway

“…Considerable work has likewise been devoted to modelling polarity establishment and gradient sensing during the yeast pheromone response (Chiou, Balasubramanian, & Lew, ). In our own work, we have integrated mathematical modelling with experimental measurements to demonstrate how reshaping of the pheromone gradient through release of the protease Bar1 is used by yeast to avoid competition for potential mating partners (Jin et al, ) and to explain the role of polarized G protein activation in tracking pheromone gradients (Kelley et al, ; McClure et al, ).…”

Optogenetics reveals Cdc42 local activation by scaffold-mediated positive feedback and Ras GTPase

“…Spatially restricted processes require polarity regulators to define discrete zones for effector protein recruitment and/or function. Feedback regulations are prevalent in cell polarization (Chiou et al, 2017;Graziano and Weiner, 2014;Kim et al, 2018). Positive and negative feedback loops within polarity modules may amplify or moderate input signals and cause dynamic competition and oscillations (Martin, 2015;Wu and Lew, 2013).…”

“…Cell morphogenesis, proliferation and differentiation all critically rely on polarized molecular cues. In metazoans and fungi, the Rho family GTPase Cdc42 is central for regulation of polarized cortical processes (Chiou et al, 2017;Etienne-Manneville, 2004;Pichaud et al, 2019). Cdc42 associates with the plasma membrane through a prenylated cysteine at the C-terminal CAAX motif and alternates between the active, GTP-bound and the inactive, GDP-bound state.…”

“…In yeast cells, where the regulation of Cdc42 is arguably best understood, Cdc42 promotes polarized cell growth in response to internal signals during the vegetative cycle and in response to external pheromone gradients during sexual reproduction (Chiou et al, 2017;Martin and Arkowitz, 2014). Fission yeast Schizosaccharomyces pombe cells express two GEFs, which are together essential to support viability (Coll et al, 2003;Hirota et al, 2003): Gef1 promotes cytokinesis and subsequent initiation of growth from the new cell end formed by the preceding cell division (Coll et al, 2007;Coll et al, 2003;Das et al, 2012;Wei et al, 2016); Scd1 is important for polarized growth during interphase (Kelly and Nurse, 2011a;Kelly and Nurse, 2011b).…”

“…Interestingly, though fission yeast cells form not one but two zones of Cdc42 activity simultaneously, in vitro data indicates that the scaffold protein Scd2 connects the GEF Scd1 to Pak1 (Chang et al, 1994;Endo et al, 2003). It remains unknown whether this complex underlies a positive feedback for the establishment of active Cdc42 zones in vivo, although this has been widely assumed in the literature Chiou et al, 2017;Das et al, 2012;Martin, 2015;Martin and Arkowitz, 2014;Tay et al, 2018). Notably, scd2 deletion causes cell rounding (Chang et al, 1994;Kelly and Nurse, 2011b) but does not severely affect Cdc42 activity, in contrast to scd1∆ , implying the existence of alternative mechanisms for Cdc42 activation.…”