Abstract
Cell size is a complex trait that responds to developmental and environmental cues. Quantitative size analysis of mutant strain collections disrupted for protein kinases and transcriptional regulators in the pathogenic yeast Candida albicans uncovered 66 genes that altered cell size, few of which overlapped with known size genes in the budding yeast Saccharomyces cerevisiae. A potent size regulator specific to C. albicans was the conserved p38/HOG MAPK module that mediates the osmostress response. Basal HOG activity inhibited the SBF G1/S transcription factor complex in a stress-independent fashion to delay the G1/S transition. The HOG network also governed ribosome biogenesis through the master transcriptional regulator Sfp1. Hog1 bound to the promoters and cognate transcription factors for ribosome biogenesis regulons and interacted genetically with the SBF G1/S machinery, and thereby directly linked cell growth and division. These results illuminate the evolutionary plasticity of size control and identify the HOG module as a nexus of cell cycle and growth regulation.
Highlights
A central and longstanding problem in cell biology is how cells maintain a uniform cell size, whether in single-celled organisms or in the multitude of tissues of metazoans [1, 2]
To address the problem of cell size control across different species, we performed the first quantitative survey of the size phenome in the pathogenic yeast Candida albicans by focusing on mutants disrupted for protein kinases and transcriptional regulators
We investigate one of the divergent size regulatory pathways in C. albicans, the p38/HOG MAPK module, to uncover a novel stress-independent
Summary
A central and longstanding problem in cell biology is how cells maintain a uniform cell size, whether in single-celled organisms or in the multitude of tissues of metazoans [1, 2]. Attainment of a critical cell size is necessary for commitment to cell division in late G1 phase, called Start in yeast and the Restriction Point in metazoans. This critical cell size threshold coordinates cell growth with cell division to establish a homeostatic cell size [1]. The dynamic control of cell size facilitates adaptation to changing environmental conditions in microorganisms and is essential to maximize fitness [3, 4]. Cell size control is important for tissue, organ and organism size [6], and is dynamically regulated through changes in growth rate and cell cycle length [7]. A loss of cell size homeostasis, termed pleomorphism, correlates with poor cancer prognosis [9]
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