Whi3 regulates morphogenesis in budding yeast by enhancing Cdk functions in apical growth

Abstract

The Whi3 protein is associated with the endoplasmic reticulum, interacts with Cdc28, the budding-yeast Cdk, binds the mRNA of cyclin CLN3 and prevents accumulation of the Cdc28-Cln3 in the nucleus until late G 1 . Besides its function as a cell size regulator, Whi3 is strictly required for filamentous growth. Here we show that emerging buds in Whi3-deficient cells are considerably rounder than in wild-type cells, indicating that Whi3 is required to maintain apical growth during S phase. This defect was not suppressed by deletion of CLB2, which is involved in switching from polar to isotropic bud growth, indicating that the observed phenotype is not the result of Whi3 acting solely as a negative regulator of cyclin Clb2. However, Cdc28 did not properly accumulate at the bud tip during S phase in whi3Δ cells, and their elongation defects were suppressed by CLN2 overexpression, suggesting a positive function for Whi3 in a Cdk-cyclin-dependent step required for apical growth. Additionally, the actin cytoskeleton was perturbed in Whi3-deficient cells, and WHI3 showed genetic interactions with actin patch components. Our results point to Whi3 as a key modulator of apical growth effectors to coordinate cell cycle events and morphogenesis. We propose that Whi3 is required for the apical localization of Cdc28-Cln1,2 complexes during bud growth and thereby, to promote the activation of Cdc42 and its effectors in the bud apex.

The promoter of filamentation (POF1) protein from Saccharomyces cerevisiae is an ATPase involved in the protein quality control process

“…For the majority of pathogenic fungi, this transformation is an essential step in their infectious process, and modifications in plasma membrane and cell wall constituents have been implicated [40,41]. The mechanisms that trigger the transition to filamentous growth in S. cerevisiae are associated with carbon or nitrogen stresses [39,42]. The interplay between the filamentation process and protein quality control may be an important feature that deserves to be further investigated.…”

The Regulation of Filamentous Growth in Yeast

“…The MAPK pathway regulates the expression of the cyclin CLN1, which encodes a G 1 cyclin . The different G 1 cyclins have different effects on the filamentation response (Loeb et al 1999;Colomina et al 2009). Elements of the morphogenetic checkpoint (Lew and Reed 1995) including the protein kinase Swe1 (Sia et al 1998;La Valle and Wittenberg 2001) are also important for filamentous growth regulation.…”

The Yak1 Protein Kinase Lies at the Center of a Regulatory Cascade Affecting Adhesive Growth and Stress Resistance inSaccharomyces cerevisiae

“…WHI3 is further involved in several developmental events, including mating and adhesive growth of haploid strains as well as filament formation and meiosis of diploids (Mö sch and Fink 1997; Gari et al 2001). Global studies have identified a large number of mRNAs that are bound by the Whi3 RRM domain (Colomina et al 2008(Colomina et al , 2009. A significant fraction of these Whi3 targets encode membrane and exocytic proteins involved in transport and cell wall biogenesis, indicating that Whi3 might be a general modulator of protein fate that affects cell integrity and organization of the actin cytoskeleton.…”