Regulation of Bud Emergence by a MAPK Pathway

Abstract

All cells establish and maintain an axis of polarity that is critical for cell shape and progression through the cell cycle. A well-studied example of polarity establishment is bud emergence in yeast, where the Rho GTPase Cdc42p regulates symmetry breaking at bud sites and the establishment of polarity by interacting with effector proteins. The prevailing view of bud emergence does not account for regulation by extrinsic cues or signal transduction pathways. Here, we show that the MAPK pathway that controls filamentous growth (fMAPK pathway), which also requires Cdc42p and the effector p21 activated kinase (PAK) Ste20p, regulates bud emergence under nutrient-limiting conditions that favor filamentous/invasive growth. The fMAPK pathway regulated the expression of polarity targets that included the gene encoding a direct effector of Cdc42p, Gic2p. The fMAPK pathway also stimulated GTP-Cdc42p levels, which is a critical determinant of polarity establishment. The fMAPK pathway activity was spatially restricted to bud sites and highest at a period in the cell cycle that coincided with bud emergence. Time-lapse fluorescence microscopy showed that the fMAPK pathway stimulated the rate of bud emergence during filamentous growth. Unregulated activation of the fMAPK pathway induced growth at multiple sites that resulted from multiple rounds of symmetry breaking inside the growing bud. Collectively, our findings identify a new regulatory aspect of bud emergence that sensitizes this essential cellular process to external cues.

Functions for Cdc42p BEM adaptors in regulating a differentiation-type MAP kinase pathway

“…Given that the fMAPK pathway is induced under nutrient-limiting conditions, one possibility is that derepression of glucose-repressed genes may be required for fMAPK function (Carlson, 1999). In a related study from our lab (Prabhakar et al, 2019), we show that the fMAPK pathway is regulated throughout the cell cycle and peaks in G 2 /M phase. Cell synchronization experiments also showed that the fMAPK pathway is activated (in G 2 /M) to the same levels as the mating and HOG pathways.…”

Functions for Cdc42p BEM Adaptors in Regulating a Differentiation-Type MAP Kinase Pathway

“…Given that the fMAPK pathway is induced under nutrient-limiting conditions, one possibility is that derepression of glucose-repressed genes ( 138 ) may be required for fMAPK function. In a related study from our lab ( 139 ), we show that the fMAPK pathway is regulated throughout the cell cycle and peaks in G 2 /M phase. Cell synchronization experiments also showed that the fMAPK pathway is activated (in G 2 /M) to the same levels as the mating and HOG pathways.…”