Regulation of Cdc42 protein turnover modulates the filamentous growth MAPK pathway

• Published in: The Journal of cell biology Vol. 221; no. 12; p. 1
• Main Authors: González, Beatriz, Cullen, Paul J
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05-12-2022
• Subjects: Adaptor proteins; Biochemistry; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - genetics; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - metabolism; Cdc42 protein; Cell Signaling; Guanosine triphosphatases; Hsp40 protein; Hsp70 protein; MAP kinase; MAP Kinase Signaling System; Polarity; Proteasomes; Protein turnover; Proteins; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction; Signaling; Ubiquitin; Ubiquitin-protein ligase; Yeasts
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.202112100

Rho GTPases are central regulators of cell polarity and signaling. How Rho GTPases are directed to function in certain settings remains unclear. Here, we show the protein levels of the yeast Rho GTPase Cdc42p are regulated, which impacts a subset of its biological functions. Specifically, the active conformation of Cdc42p was ubiquitinated by the NEDD4 ubiquitin ligase Rsp5p and HSP40/HSP70 chaperones and turned over in the proteasome. A GTP-locked (Q61L) turnover-defective (TD) version, Cdc42pQ61L+TD, hyperactivated the MAPK pathway that regulates filamentous growth (fMAPK). Cdc42pQ61L+TD did not influence the activity of the mating pathway, which shares components with the fMAPK pathway. The fMAPK pathway adaptor, Bem4p, stabilized Cdc42p levels, which resulted in elevated fMAPK pathway signaling. Our results identify Cdc42p turnover regulation as being critical for the regulation of a MAPK pathway. The control of Rho GTPase levels by stabilization and turnover may be a general feature of signaling pathway regulation, which can result in the execution of a specific developmental program.