Regulation of cell polarity by control of Sut1-mediated gene expression via the Cdc42 effectors Ste20, Cla4 and Skm1

• Applicant: Professor Dr. Stefan Rose-John, since 4/2010
• Subject Area: Cell Biology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 95085825

Rho-type GTPases such as Cdc42 play a key role in cell polarity. Among the Cdc42 effectors in budding yeast are the PAK-family kinases Ste20, Cla4 and Skm1. Previously, we could demonstrate that Ste20 not only localizes to sites of polarized growth but also translocates into the nucleus. There it interacts with the transcriptional regulator Sut1 and down-regulates the expression of the Sut1 targets AUS1 and DAN1, an ABC transporter and a cell wall protein, respectively, which promote sterol uptake. We could further show that Skm1 localizes to the nucleus, although its function remains unclear. Moreover, Sut1 binds to the promoter regions of genes involved in cell polarity (RHO3, RHO5, MGA1 and PRR2). Therefore, it is conceivable that Ste20, Cla4 and Skm1 establish cell polarity by regulating gene expression via Sut1. The aim of this project is a detailed analysis of this process. It will be tested whether Skm1 and Cla4, like Ste20, interact with Sut1 and regulate the expression of DAN1 and AUS1. Further, the role of the nuclear translocation of Ste20 for its various functions will be analyzed. In addition, we plan to examine whether and how Sut1, Ste20, Skm1 and Cla4 contribute to the expression of RHO3, RHO5, MGA1 and PRR2. Finally, the molecular mechanisms of the regulation of Sut1 activity by PAK-family kinases will be analyzed.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Thomas Höfken, until 3/2010