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Cdc42p-interacting protein Bem4p regulates the filamentous-growth mitogen-activated protein kinase pathway
Andrew Pitoniak1, Colin A Chavel1, Jacky Chow1
1Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Abstract:
The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different settings to regulate cell polarity and cellular signaling. How Cdc42p and other proteins are directed to function in a particular context remains unclear. We show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated protein kinase (MAPK) pathway that controls filamentous growth in Saccharomyces cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK pathways (mating or high-osmolarity glycerol response [HOG]) that also require Cdc42p and other shared components. Bem4p associated with the plasma membrane (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF) Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in an autoinhibitory capacity, and was required, along with other pathway regulators, to maintain Cdc24p at polarized sites during filamentous growth. Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is a new regulator of the filamentous-growth MAPK pathway and binds to general proteins, like Cdc42p and Ste11p, to promote a pathway-specific response.
Insights
Bem4p protein specifically regulates the filamentous growth pathway in yeast by interacting with key signaling proteins. This interaction ensures pathway specificity for cell polarity and signaling under nutrient limitation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The Rho GTPase Cdc42p is crucial for cell polarity and signaling but its context-specific functions are not fully understood.
- Understanding how proteins like Cdc42p are directed to specific cellular pathways is essential for comprehending cellular regulation.
Purpose of the Study:
- To investigate the role of Cdc42p-interacting protein Bem4p in regulating specific cellular pathways.
- To elucidate the mechanism by which Bem4p confers specificity to mitogen-activated protein kinase (MAPK) pathways.
Main Methods:
- Yeast genetics and molecular biology techniques were employed.
- Protein-protein interaction studies, including association with plasma membrane proteins and guanine nucleotide exchange factors, were performed.
- Analysis of MAPK pathway activation and protein localization during filamentous growth was conducted.
Main Results:
- Bem4p specifically regulates the filamentous growth MAPK pathway, distinct from mating and high-osmolarity glycerol response (HOG) pathways.
- Bem4p associates with Sho1p at the plasma membrane, influencing MAPK activity and cell polarization.
- Bem4p interacts with Cdc24p and Ste11p, contributing to Cdc24p localization and filamentous growth pathway activation.
Conclusions:
- Bem4p is identified as a novel regulator of the filamentous growth MAPK pathway in Saccharomyces cerevisiae.
- Bem4p's interaction with general signaling proteins like Cdc42p and Ste11p promotes pathway-specific responses.
- Bem4p plays a critical role in directing Cdc42p-mediated signaling towards filamentous growth under specific environmental conditions.
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