Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.11.24.690177

A CROSS-SPECIES ANALYSIS OF CELL WALL MECHANOSENSORS

Abstract

The cell wall (CW) protects fungal cells from various mechanical challenges making its integrity essential for cell survival. CW integrity is monitored by transmembrane sensors that activate downstream effectors to promote CW synthesis in response to injuries. Sensors of the WSC family are found in most fungi, and share a conserved architecture, with a cytoplasmic tail, a single transmembrane domain and a long Serine Threonine Rich domain (STR) prolonged by a WSC domain, both embedded in the CW. In response to forces applied onto the CW, these extracellular domains promote force detection, sensor clustering and cell survival. Interestingly, Wsc sensors exhibit variations in domain sequence and size among different fungal species. To understand how these variations impact mechanosensing, we heterologously expressed Wsc sensors taken from S. cerevisiae and C. albicans, in the fission yeast S. pombe. Remarkably, we found that a subset of these foreign sensors could cluster at sites of CW compression, but that others failed, suggesting divergences in mechanosensing abilities. By swapping sensor domains, we demonstrate that both the cytoplasmic tail and STR influence mechanosensation. These findings reveal a high level of functional plasticity in fungal sensors, and identify tuneable modules that may regulate mechanosensing of various CWs. SIGNIFICANCE STATEMENTO_LICell Wall Mechanosensors of the WSC family are present in most fungi, but whether they can detect mechanical stimuli in a foreign cell wall of a distant fungal species is unknown. C_LIO_LIThe authors heterologously expressed Wsc sensors taken from S. cerevisiae and C. albicans in the fission yeast S. pombe and demonstrate that a subset of foreign sensors can probe mechanical stress in its Cell Wall. C_LIO_LIThis work highlights a remarkable plasticity in mechanosensors ability to detect mechanical stress in the Cell Wall and identifies domains involved in regulating mechanosensing. C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Municio-Diaz, C., MINC, N.. 2025-11-25. A CROSS-SPECIES ANALYSIS OF CELL WALL MECHANOSENSORS. https://doi.org/10.1101/2025.11.24.690177

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Differential requirement for the Ire1 luminal domain in Candida albicans drug susceptibility and pathogenicity

The opportunistic human pathogen Candida albicans depends on the unfolded protein response (UPR) for cell wall integrity, antifungal tolerance, filamentous growth, and virulence. The UPR is driven by the conserved transmembrane sensor Ire1, which is activated either by misfolded proteins through its luminal domain or by lipid bilayer stress (LBS) through its transmembrane domain. In budding yeast, these two activation modes deploy divergent transcriptional programs. Whether the requirement for these two input domains is separable in C. albicans, where the cell membrane and cell wall are themselves the targets of major antifungal drug classes, remains unknown. Here, we engineered a C. albicans strain expressing Ire1 lacking an intact luminal domain (ire1{Delta}LD), which no longer detects proteotoxic stress. The ire1{Delta}LD strain grew in the presence of the azole antifungals fluconazole and miconazole but was highly sensitive to heat shock, cell wall stress, and the echinocandin caspofungin. It was also unable to sustain filamentous growth and showed reduced virulence in a Caenorhabditis elegans infection model. RNA sequencing revealed only modest changes to the steady-state transcriptome of ire1{Delta}LD cells. Together, these findings define a differential requirement for the input domains of C. albicans Ire1, uncoupling growth under azole-induced membrane stress from the cell wall, thermal, and virulence-associated outputs that depend on proteotoxic sensing, a distinction that could inform antifungal strategies targeting the UPR.

cell biology↗

Nucleosome Core Allostery Governs Chromatin Recognition and Cell Fate

Nucleosomes regulate chromatin folding, accessibility, and factor recruitment. Current models primarily attribute these functions to histone tail modifications, while the core is largely viewed as a structural scaffold. Yet subtle changes within the nucleosome core can produce profound functional consequences, and the mechanisms underlying these effects remain unclear. Here, we describe nucleosome core allostery as a fundamental principle of chromatin regulation that amplifies the impact of minimal nucleosome variations. Leveraging natural differences between H2A.Z variants, we show that the nucleosome core encodes distinct conformational dynamics that propagate allosterically, thereby controlling nucleosome accessibility and recognition by chromatin factors. As a result, a single buried amino acid substitution alone is sufficient to reprogram nucleosome dynamics and bias cell identity. Our findings establish the nucleosome core as an allosteric regulatory module and provide a generalizable framework for how subtle variation within nucleosomes is amplified into diverse biological outcomes in development and disease.

cell biology↗

YAP/TAZ-controlled ERK dynamics coordinate progenitor expansion and differentiation commitment

Progenitor cells must proliferate to expand the cell population, yet terminal differentiation requires this proliferative state to end. How signaling controls the duration of this proliferative window remains poorly understood. Using adipogenesis and live single-cell imaging of differentiation, cell-cycle, and ERK-activity reporters, we show that YAP and TAZ coordinate progenitor expansion with differentiation commitment by regulating ERK dynamics. YAP/TAZ maintain cells in a fluctuating high-ERK state that promotes proliferation while actively keeping the differentiation driver PPARG below the threshold for irreversible commitment. Crucially, this differentiation block is not explained by proliferation alone: inhibiting CDK4/6 or AKT suppressed proliferation without restoring differentiation, whereas MEK-ERK inhibition restored differentiation even when YAP/TAZ activity remained high. As YAP/TAZ activity decreases, dampened ERK fluctuations trigger PPARG activation. These findings support a self-limiting model in which YAP/TAZ-driven progenitor expansion progressively increases cell density and contact-dependent Hippo signaling, reducing YAP/TAZ activity and terminating the proliferative phase. Consequently, transient YAP/TAZ activation expands the progenitor pool while preserving subsequent differentiation, whereas sustained activation suppresses commitment. Together, these findings identify YAP/TAZ-controlled ERK dynamics as the nexus coordinating progenitor expansion with terminal differentiation and suggest that slower density-dependent Hippo feedback may set the duration of this proliferative window to regulate differentiated cell-number output.

cell biology↗