Secretory Pathway-Dependent Localization of the Saccharomyces cerevisiae Rho GTPase-Activating Protein Rgd1p at Growth Sites

Lefèbvre, Fabien; Prouzet‐Mauléon, Valérie; Hugues, Michel; Crouzet, Marc; Vieillemard, Aurélie; McCusker, Derek; Thoraval, Didier; Doignon, François

doi:10.1128/ec.00042-12

Cited by 10 publications

(10 citation statements)

References 86 publications

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“…Given this unique resemblance among mammalian F-BAR domains to Rgd1p, it is intriguing that Gmip, like Rgd1p, is also a Rho-GAP, specific for RhoA (Aresta et al, 2002). This correspondence may signal an analogous functional dependence on phosphoinositides in the related functions of these yeast and mammalian Rho-GAPs that have been documented in the secretory pathway (Johnson et al, 2012; Lefèbvre et al, 2012). Gmip has also been reported to play important roles in cortical actin remodeling in early mitosis (Andrieu et al, 2014) and the speed of neuronal migration in the postnatal brain (Ota et al, 2014) – both processes in which phosphoinositides are likely to play an important regulatory role.…”

Section: Resultsmentioning

confidence: 55%

“…We identified one F-BAR domain – from S. cerevisiae Rgd1p – in a screen of yeast proteins that specifically recognize phosphoinositides (Moravcevic et al, 2010). Rgd1p is a GTPase-activating protein (GAP) specific for the Rho3 and Rho4 small GTPases, which control actin cytoskeleton organization and stress signaling pathways (Doignon et al, 1999; Lefèbvre et al, 2012; Roumanie et al, 2000). …”

Section: Introductionmentioning

confidence: 99%

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Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

et al. 2015

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SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence.

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Section: Resultsmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

et al. 2015

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“…Cargo with Bgl2p should be specifically targeted to regions of active growth. We deduced from our results that (i) PI(4,5)P 2 with stearic acid (C 18:0 ) and palmitic acid (C 16:0 ) giving rise to PIP2 34:0, (ii) PI(4,5)P 2 with oleic acid (C 18:1 ) giving rise to PIP2 36:1, or (iii) PI(4,5)P 2 with palmitoleic acid (C 16:1 ) giving rise to PIP2 34:1 is essential to control the late steps of trafficking by interacting with many mediators of polarization operating partly with the exocyst, such as Cdc24p (a GEF of Cdc42p), Rom2p (the GEF of Rho1p), Sec3p (72,73), and Rgd1p (the Rho GTPase-activating protein [RhoGAP] for Rho3p) (74)(75)(76). Moreover, the essential functions of Cdc42p and Rho1p rely on their binding to PI(4,5)P 2 , thus increasing the levels of such GTPases at specific sites (68,77).…”

Section: Fig 13mentioning

confidence: 99%

Requirement of Phosphoinositides Containing Stearic Acid To Control Cell Polarity

Doignon

Laquel

Testet

et al. 2016

Molecular and Cellular Biology

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c Phosphoinositides (PIPs) are present in very small amounts but are essential for cell signaling, morphogenesis, and polarity. By mass spectrometry, we demonstrated that some PIPs with stearic acyl chains were strongly disturbed in a psi1⌬ Saccharomyces cerevisiae yeast strain deficient in the specific incorporation of a stearoyl chain at the sn-1 position of phosphatidylinositol. The absence of PIPs containing stearic acid induced disturbances in intracellular trafficking, although the total amount of PIPs was not diminished. Changes in PIPs also induced alterations in the budding pattern and defects in actin cytoskeleton organization (cables and patches). Moreover, when the PSI1 gene was impaired, a high proportion of cells with bipolar cortical actin patches that occurred concomitantly with the bipolar localization of Cdc42p was specifically found among diploid cells. This bipolar cortical actin phenotype, never previously described, was also detected in a bud9⌬/bud9⌬ strain. Very interestingly, overexpression of PSI1 reversed this phenotype. Lipids are not limited to the simple role of being components of biological membranes for cell compartmentalization. On the basis of their structural diversity, they are also biologically active molecules regulating several important physiological functions. Lipids can be classified into eight broad categories, on the basis of well-defined chemical and biochemical principles, with distinct functions in cells (1). Among them, phosphatidylinositol-4-phosphate [PI(4)P] and phosphatidylinositol-4,5-diphosphate [PI(4,5)P 2 ], derived from phosphatidylinositol (PI) by a series of kinase reactions, play major roles, even though they are minor constituents of cellular membranes; e.g., in the yeast Saccharomyces cerevisiae, PI represents about 20% of total phospholipids (2) and phosphatidylinositol phosphates (PIPs) represent only 0.1 to 1.1% of PIs (3, 4). It has been established that some mutations in genes encoding PIP-metabolizing enzymes are responsible for human diseases (Lowe syndrome, myopathy, Charcot-Marie-Tooth disease, psychiatric diseases, diabetes, cancer, Alzheimer's disease, etc.) (5). In addition, previous studies have demonstrated the role of PIPs in the control of cell polarity (by acting on actin cytoskeleton dynamics), secretory pathways, and septin recruitment and organization in animals, plants, and yeasts (6-11). Nevertheless, most studies pointing out a specific role for PIPs are related to the polar head groups and not to the fatty acid component, even though PIs from plants, animals, and yeast contain larger amounts of saturated fatty acids than other phospholipids (12). Only a few studies have highlighted the importance of the acyl chain composition of PIPs, for example, the nature of the acyl chains associated with PI(4,5)P 2 for activation of the GIRK1/GIRK4 potassium channel (13,14), and the importance of saturated fatty acids associated with PIPs to address these lipids in plant lipid rafts (15). In S. cerevisiae, stearic acid accounts for a few p...

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“…Three of the RhoGAP proteins, Rgd1, Rgd2, and Rgd3 also contain an F-BAR domain that implies they likely associate with moderately curved membranes. Rgd1, a RhoGAP for Rho3 and Rho4, has been shown to localize to polarized vesicles consistent with post-Golgi secretory vesicles (Lefèbvre et al, 2012;Doignon et al, 1999). Rgd2, a RhoGAP for Cdc42 and Rho5, localized to the bud tip in a high-throughput genomic screen (Dubreuil et al, 2018;Roumanie et al, 2001).…”

Section: Discussionmentioning

confidence: 91%

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Gingras

Lwin

Miller

et al. 2020

Preprint

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Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4dependent transport of secretory vesicles to sites of polarized growth. Over-expression suppressors of a conditional myo2 smy1 mutant identified a novel F-BAR-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 overexpression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function. In vitro Rgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho-state and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in the myo2 smy1 mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.

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Secretory Pathway-Dependent Localization of the Saccharomyces cerevisiae Rho GTPase-Activating Protein Rgd1p at Growth Sites

Cited by 10 publications

References 86 publications

Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

Requirement of Phosphoinositides Containing Stearic Acid To Control Cell Polarity

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

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