The Cdc42 effectors ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway

Lin, Meng; Unden, Heike; Jacquier, Nicolas; Schneiter, Roger; Just, Ursula; Höfken, Thomas

doi:10.1091/mbc.E09-01-0034

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The Cdc42 effectors ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway

Lin, Meng Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
Unden, Heike Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
Jacquier, Nicolas Division of Biochemistry, University of Fribourg, Switzerland
Schneiter, Roger Division of Biochemistry, University of Fribourg, Switzerland
Just, Ursula Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
Höfken, Thomas Institute of Biochemistry, Christian Albrecht University, Kiel, Germany

30.09.2009

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Molecular Biology of the Cell. - 2009, vol. 20, no. 22, p. 4826-4837

English In Saccharomyces cerevisiae, the Rho-type GTPase Cdc42 regulates polarized growth through its effectors, including the p21-activated kinases (PAKs) Ste20, Cla4, and Skm1. Previously, we demonstrated that Ste20 interacts with several proteins involved in sterol synthesis that are crucial for cell polarization. Under anaerobic conditions, sterols cannot be synthesized and need to be imported into cells. Here, we show that Ste20, Cla4, and Skm1 form a complex with Sut1, a transcriptional regulator that promotes sterol uptake. All three PAKs can translocate into the nucleus and down-regulate the expression of genes involved in sterol uptake, including the Sut1 targets AUS1 and DAN1 by a novel mechanism. Consistently, deletion of either STE20, CLA4, or SKM1 results in an increased sterol influx and PAK overexpression inhibits sterol uptake. For Ste20, we demonstrate that the down-regulation of gene expression requires nuclear localization and kinase activity of Ste20. Furthermore, the Ste20-mediated control of expression of sterol uptake genes depends on SUT1 but is independent of a mitogen-activated protein kinase signaling cascade. Together, these observations suggest that PAKs translocate into the nucleus, where they modulate expression of sterol uptake genes via Sut1, thereby controlling sterol homeostasis.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

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