Exploring roles for essential proteins in yeast filamentous growth identifies the WASP homolog Las17 as a regulator of the Cdc42-dependent fMAPK pathway
- 1University at Buffalo
Abstract
Cell differentiation into distinct cell types generates functional specialization in eukaryotic organisms. Many fungal species undergo filamentous growth, where cells differentiate into elongated and adhesive filaments capable of expansion and invasion into new environments. The budding yeast Saccharomyces cerevisiae also undergoes filamentous growth, and the regulatory pathways that control the response have been well characterized; however, the roles essential proteins play in this response have not been systematically explored. To address this gap in understanding, we constructed a collection of 332 temperature-sensitive (ts) alleles in 320 essential genes in a strain background that undergoes filamentous growth (called {Sigma}1278b or Sigma). The ts Sigma collection showed differences in temperature sensitivity compared to a ts laboratory strain collection, revealing unexpected phenotypic diversity in essential alleles across populations of individuals. Screening the ts Sigma collection for phenotypes related to filamentous growth uncovered new phenotypes for >35% of essential alleles. New regulators of the Mitogen-Activated Protein Kinase (MAPK) pathway that regulates filamentous growth (fMAPK) were identified, including Las17, a homolog of Wiskott-Aldrich Syndrome Protein (WASP) in humans. Las17 regulated the fMAPK pathway by promoting delivery of the sensor protein, Sho1, and Rho GTPase Cdc42 to the plasma membrane. Las17 also functioned as a hub coordinating separate parallel aspects of the filamentation response. The widespread roles for essential proteins in regulating a eukaryotic differentiation response suggest broader roles essential proteins than is currently appreciated.
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BibTeX
@misc{pujari2026exploring,
title = {{Exploring roles for essential proteins in yeast filamentous growth identifies the WASP homolog Las17 as a regulator of the Cdc42-dependent fMAPK pathway}},
author = {A. N. Pujari and A. Priyadarshini and Z. Li and A. S. Darekar and D. Williams and D. Climie and S. Bahr and H. Friesen and M. Li and J. M. Oken and R. M. Romito and B. J. Andrews and C. Boone and P. J. Cullen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.751561},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.751561v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Exploring roles for essential proteins in yeast filamentous growth identifies the WASP homolog Las17 as a regulator of the Cdc42-dependent fMAPK pathway
AU - A. N. Pujari
AU - A. Priyadarshini
AU - Z. Li
AU - A. S. Darekar
AU - D. Williams
AU - D. Climie
AU - S. Bahr
AU - H. Friesen
AU - M. Li
AU - J. M. Oken
AU - R. M. Romito
AU - B. J. Andrews
AU - C. Boone
AU - P. J. Cullen
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.751561
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.751561v1
AB - Cell differentiation into distinct cell types generates functional specialization in eukaryotic organisms. Many fungal species undergo filamentous growth, where cells differentiate into elongated and adhesive filaments capable of expansion and invasion into new environments. The budding yeast Saccharomyces cerevisiae also undergoes filamentous growth, and the regulatory pathways that control the response have been well characterized; however, the roles essential proteins play in this response have not been systematically explored. To address this gap in understanding, we constructed a collection of 332 temperature-sensitive (ts) alleles in 320 essential genes in a strain background that undergoes filamentous growth (called {Sigma}1278b or Sigma). The ts Sigma collection showed differences in temperature sensitivity compared to a ts laboratory strain collection, revealing unexpected phenotypic diversity in essential alleles across populations of individuals. Screening the ts Sigma collection for phenotypes related to filamentous growth uncovered new phenotypes for >35% of essential alleles. New regulators of the Mitogen-Activated Protein Kinase (MAPK) pathway that regulates filamentous growth (fMAPK) were identified, including Las17, a homolog of Wiskott-Aldrich Syndrome Protein (WASP) in humans. Las17 regulated the fMAPK pathway by promoting delivery of the sensor protein, Sho1, and Rho GTPase Cdc42 to the plasma membrane. Las17 also functioned as a hub coordinating separate parallel aspects of the filamentation response. The widespread roles for essential proteins in regulating a eukaryotic differentiation response suggest broader roles essential proteins than is currently appreciated.
ER -