Functions for Cdc42p BEM adaptors in regulating a differentiation-type MAP kinase pathway
Sukanya Basu1, Beatriz González1, Boyang Li1
1Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260.
Molecular Biology of the Cell
|January 16, 2020
Summary
This study reveals unique roles for Rho GTPase adaptors Bem4p and Bem1p in regulating the filamentous growth mitogen-activated protein kinase (fMAPK) pathway in yeast. Findings highlight sequential adaptor functions in controlling cell polarity and MAPK signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Ras homology (Rho) GTPases, like Cdc42p in yeast, are crucial regulators of cell polarity and signal transduction.
- Cdc42p influences multiple mitogen-activated protein kinase (MAPK) pathways, including mating, filamentous growth (fMAPK), and high osmolarity glycerol (HOG).
- The precise mechanisms by which Cdc42p regulates the fMAPK pathway remain incompletely understood.
Purpose of the Study:
- To elucidate the specific roles of Cdc42p adaptors, Bem4p and Bem1p, in regulating the yeast fMAPK pathway.
- To compare the activation kinetics of different Cdc42p-dependent MAPK pathways.
- To identify key interactions and domains within Bem4p and Bem1p essential for fMAPK signaling.
Main Methods:
- Comparative analysis of MAPK pathway activation profiles in a filamentous yeast strain.
- Site-directed mutagenesis to assess the function of specific Cdc42p and Bem4p residues.
- Investigation of Bem1p mutants defective in plasma membrane recruitment, intramolecular interactions, and GEF interaction.
- Genetic suppression tests to determine the order of Bem4p and Bem1p function.
Main Results:
- The fMAPK pathway exhibits slower activation kinetics compared to mating and HOG pathways.
- Cdc42pE100A, defective in fMAPK signaling, shows impaired interaction with the adaptor Bem4p.
- Specific Bem4p residues are critical for Cdc42p interaction and fMAPK pathway signaling.
- Bem1p's function in the fMAPK pathway depends on its ability to recruit Ste20p, its intramolecular interactions, and its interaction with the GEF Cdc24p.
- Bem4p and Bem1p function sequentially in regulating the fMAPK pathway.
Conclusions:
- Rho GTPase adaptors exhibit unique and sequential functions in regulating distinct MAPK pathways.
- Bem4p and Bem1p play critical, ordered roles in the Cdc42p-dependent fMAPK signaling cascade.
- Understanding these adaptor functions provides insight into the complex regulation of cell polarity and morphogenesis.
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