Homologues of Oxysterol‐Binding Proteins Affect Cdc42p‐ and Rho1p‐Mediated Cell Polarization in <i>Saccharomyces cerevisiae</i>

Kozminski, Keith G.; Alfaro, Gabriel; Dighe, Shubha; Beh, Christopher T.

doi:10.1111/j.1600-0854.2006.00467.x

Cited by 63 publications

(121 citation statements)

References 133 publications

(188 reference statements)

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“…The actin-dependent Cdc42 polarization was also confirmed by studies using antibodies against endogenous Cdc42 (Irazoqui et al 2005;Zajac et al 2005;Kozminski et al 2006). Mathematical simulation using the yeast system supports the hypothesis that local activation of Cdc42, subsequent actin polymerization through downstream Cdc42 effectors, and vesicular transport provide a positive feedback loop that leads to cell polarization (Wedlich-Soldner et al 2003).…”

Section: Polarization Of Cdc42 By Membrane Traffic In Budding Yeastmentioning

confidence: 55%

Membrane Organization and Dynamics in Cell Polarity

Orlando¹,

Guo²

2009

Cold Spring Harbor Perspectives in Biology

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The establishment and maintenance of cell polarity is important to a wide range of biological processes ranging from chemotaxis to embryogenesis. An essential feature of cell polarity is the asymmetric organization of proteins and lipids in the plasma membrane. In this article, we discuss how polarity regulators such as small GTP-binding proteins and phospholipids spatially and kinetically control vesicular trafficking and membrane organization. Conversely, we discuss how membrane trafficking contributes to cell polarization through delivery of polarity determinants and regulators to the plasma membrane.

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Section: Polarization Of Cdc42 By Membrane Traffic In Budding Yeastmentioning

confidence: 55%

Membrane Organization and Dynamics in Cell Polarity

Orlando¹,

Guo²

2009

Cold Spring Harbor Perspectives in Biology

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“…Thus, it seems that Cla4 modulates sterol homeostasis under aerobic conditions and that all PAKs are involved in sterol import under anaerobiosis. In addition, homologues of oxysterol-binding proteins, a family of proteins, which regulate synthesis and transport of sterols, were found to participate in Cdc42-dependant cell polarity (Kozminski et al, 2006). How sterols contribute to cell polarization has been discussed controversially (Pichler and Riezman, 2004;Alvarez et al, 2007), and the elucidation of underlying molecular mechanisms will require further work.…”

Section: Discussionmentioning

confidence: 99%

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

Unden

Jacquier

et al. 2009

MBoC

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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. INTRODUCTIONThe small Rho GTPase Cdc42 plays a central role in the regulation of cellular polarity in eukaryotic cells (EtienneManneville, 2004;Jaffe and Hall, 2005). In the budding yeast Saccharomyces cerevisiae, Cdc42 regulates different types of polarized growth during various phases of its life cycle, including budding during vegetative growth, mating between haploid cells of opposite mating types, and filamentous growth upon nutrient limitation (Park and Bi, 2007). Cdc42 promotes polarized growth through multiple pathways, including polarization of the actin cytoskeleton and directed vesicle trafficking. Among the Cdc42 effectors that trigger these pathways are Ste20, Cla4 and Skm1, members of the p21-activated kinase (PAK) family of serine/threonine protein kinases (Hofmann et al., 2004;Park and Bi, 2007).Cdc42 recruits Ste20 and Cla4 from the cytoplasm and activates them at the plasma membrane at sites of polarized growth. Therefore, Ste20 and Cla4 are enriched at tips of buds and mating projections (Peter et al., 1996;Leberer et al., 1997;Holly and Blumer, 1999). The recruitment of Ste20 and Cla4 to these sites is governed by protein-protein as well as protein-lipid interactions. PAKs carry a conserved Cdc42/ Rac-interactive binding (CRIB) domain that mediates binding to Cdc42 and regulates their activity (Cvrckova et al., 1995;Peter et al., 1996;Leberer et al., 1997;Lamson et al., 2002;Ash et al., 2003). Ste20 and Cla4 also bind to Bem1, a scaffold protein that brings Cdc42, its activator Cdc24 and either Ste20 or Cla4, into proximity (Leeuw et al., 1998;Gulli et al., 2000;Bose et al., 2001;Yamaguchi et al., 2007). In addition, phosphoinositide-binding domains promote the association with membrane lip...

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“…After the exocyst complex attaches a vesicle to the PM, membrane fusion ensues. In the absence of all OSH gene function, undocked vesicles accumulate within buds, as observed either by electron microscopy (27) or when vesicles marked with GFP-Sec4p are tracked in vivo (32,46). An in vivo assay of polarized exocytosis, using ␤-1,3-glucanase (Bgl2p) as a marker of vesicular transport (47), affirmed that major defects in polarized exocytosis result after Osh protein inactivation (46).…”

Section: Osh Proteins Promote Vesicle/pm Tetheringmentioning

confidence: 99%

“…In the absence of all OSH gene function, undocked vesicles accumulate within buds, as observed either by electron microscopy (27) or when vesicles marked with GFP-Sec4p are tracked in vivo (32,46). An in vivo assay of polarized exocytosis, using ␤-1,3-glucanase (Bgl2p) as a marker of vesicular transport (47), affirmed that major defects in polarized exocytosis result after Osh protein inactivation (46). More specifically, genetic and physical interactions directly implicate Osh proteins in the regulation of exocyst complex assembly (32,46).…”

Section: Osh Proteins Promote Vesicle/pm Tetheringmentioning

confidence: 99%

“…An in vivo assay of polarized exocytosis, using ␤-1,3-glucanase (Bgl2p) as a marker of vesicular transport (47), affirmed that major defects in polarized exocytosis result after Osh protein inactivation (46). More specifically, genetic and physical interactions directly implicate Osh proteins in the regulation of exocyst complex assembly (32,46). Many OSH genes are allele-specific suppressors of cdc42 polarized cell growth defects, and OSH genes interact with other genes encoding exocyst complex subunits.…”

Section: Osh Proteins Promote Vesicle/pm Tetheringmentioning

confidence: 99%

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A Detour for Yeast Oxysterol Binding Proteins

Beh

McMaster

Kozminski

et al. 2012

Journal of Biological Chemistry

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Oxysterol binding protein-related proteins, including the yeast proteins encoded by the OSH gene family (OSH1-OSH7), are implicated in the non-vesicular transfer of sterols between intracellular membranes and the plasma membrane. In light of recent studies, we revisited the proposal that Osh proteins are sterol transfer proteins and present new models consistent with known Osh protein functions. These models focus on the role of Osh proteins as sterol-dependent regulators of phosphoinositide and sphingolipid pathways. In contrast to their posited role as non-vesicular sterol transfer proteins, we propose that Osh proteins coordinate lipid signaling and membrane reorganization with the assembly of tethering complexes to promote molecular exchanges at membrane contact sites.

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Homologues of Oxysterol‐Binding Proteins Affect Cdc42p‐ and Rho1p‐Mediated Cell Polarization in Saccharomyces cerevisiae

Cited by 63 publications

References 133 publications

Membrane Organization and Dynamics in Cell Polarity

Membrane Organization and Dynamics in Cell Polarity

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

A Detour for Yeast Oxysterol Binding Proteins

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