Ikui, A. | Search bioRxiv

bioRxiv2026

Cell wall remodeling is required for crowding homeostasis during cell growth in S. cerevisiae

The cytoplasm is a densely crowded environment that plays essential roles in intracellular functions. Its biophysical properties can be markedly altered in response to environmental cues and changes in cellular state. Recent studies have shown that excessive growth leads to cytoplasmic dilution, contributing to cellular dysfunction. However, the molecular mechanisms regulating biophysical properties during excessive growth remain poorly understood. Here, we demonstrate that cell wall remodeling is crucial to maintain cytoplasmic crowding homeostasis during cell growth. Live-cell imaging and phosphoproteomic analysis showed that Mpk1, a component of Cell Wall Integrity (CWI) pathway, accumulates in the nucleus and its activity progressively increases as cells enlarge. Mpk1 is required to restrict cell volume expansion and maintain cytoplasmic crowding by adjusting cell wall thickness and mechanical resistance. Moreover, Mpk1 is essential for the survival of enlarged cells upon cell cycle re-entry. In addition to Mpk1, we identified multiple key components of the CWI pathway that are required to maintain physiological state of enlarged cells. Together, these findings establish the CWI signaling pathway as a key regulator of cell size homeostasis and cytoplasmic biophysical properties, providing a mechanistic link between cell wall remodeling and intracellular properties.

Cell Biology↗

bioRxiv2018

Tryptophan recovers sensitivity to cell membrane stress in Saccharomyces cerevisiae

Sodium dodecyl sulfate is a detergent that disrupts cell membranes, activates cell wall integrity signaling and restricts cell growth in Saccharomyces cerevisiae. However, the underlying mechanism of how sodium dodecyl sulfate inhibits cell growth is not fully understood. Because deletion of the MCK1 gene leads to sensitivity to sodium dodecyl sulfate, we implemented a suppressor gene screening revealing that the TAT2 tryptophan permease rescues cell growth to sodium dodecyl sulfate-treated{Delta} mck1 cells. Therefore, we questioned the involvement of tryptophan in the response to sodium dodecyl sulfate treatment. In this work, we show that{Delta} trp1 cells have a disadvantage in the response to sodium dodecyl sulfate compared to auxotrophy for adenine, histidine, leucine or uracil. While also critical in the response to tea tree oil, TRP1 does not avert growth inhibition due to other cell wall/membrane perturbations that activate cell wall integrity signaling such as calcofluor white, Congo Red or heat stress. This implicates a distinction from the cell wall integrity pathway and suggests specificity to membrane stress as opposed to cell wall stress. We discover that tyrosine biosynthesis is also essential upon sodium dodecyl sulfate perturbation whereas phenylalanine biosynthesis appears dispensable. Finally, we observe enhanced tryptophan import within minutes upon exposure to sodium dodecyl sulfate indicating that these cells are not starved for tryptophan. In summary, our results expose a functional link between internal tryptophan levels and tryptophan biosynthesis in the response to plasma membrane damage.

cell biology↗