Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers

Saint-Jean, Maud de; Delfosse, V.; Douguet, Dominique; Chicanne, Gaëtan; Payrastre, Bernard; Bourguet, William; Antonny, Bruno; Drin, Guillaume

doi:10.1083/jcb.201104062

Cited by 342 publications

(429 citation statements)

References 42 publications

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“…1b). These peaks are characteristic of DHE, which suggests fluorescence resonance energy transfer (FRET) from Upc2 LBD to bound DHE 25,26 . Upc2 LBD binds free DHE with nanomolar affinity as measured by equilibrium-binding experiments (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Fluorescent measurements of DHE binding to Upc2 LBD were based on FRET between Trp and bound DHE and were carried out using methods as previously reported 26,53 . For kinetics measurements, Trp fluorescence was measured at 340 nm (bandwidth 5 nm) on excitation at 285 nm (bandwith 5 nm) in a spectrofluorometer (FP-6200; JASCO).…”

Section: Methodsmentioning

confidence: 99%

“…DOPC, DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine), were obtained from Avanti Polar Lipids Inc. Phosphatidylinositol (soybean), ergosterol and DHE were obtained from Sigma-Aldrich. The liposomes were prepared as described with slight modifications 26 . Lipids in stock solutions in chloroform or in ethanol were mixed at the desired molar ratio, incubated at 37°C for 5 min and the solvent was evaporated by nitrogen stream.…”

Section: Methodsmentioning

confidence: 99%

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Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

et al. 2015

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Transcriptional regulation of ergosterol biosynthesis in fungi is crucial for sterol homeostasis and for resistance to azole drugs. In Saccharomyces cerevisiae, the Upc2 transcription factor activates the expression of related genes in response to sterol depletion by poorly understood mechanisms. We have determined the structure of the C-terminal domain (CTD) of Upc2, which displays a novel a-helical fold with a deep hydrophobic pocket. We discovered that the conserved CTD is a ligand-binding domain and senses the ergosterol level in the cell. Ergosterol binding represses its transcription activity, while dissociation of the ligand leads to relocalization of Upc2 from cytosol to nucleus for transcriptional activation. The C-terminal activation loop is essential for ligand binding and for transcriptional regulation. Our findings highlight that Upc2 represents a novel class of fungal zinc cluster transcription factors, which can serve as a target for the developments of antifungal therapeutics.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

et al. 2015

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“…Numerous studies also implicate Osh proteins in nonvesicular sterol transportation (Raychaudhuri et al 2006;de Saint-Jean et al 2011;Jansen et al 2011). By measuring the amount of free sterols converted to steryl esters (esterification), Raychaudhuri et al showed a sevenfold decrease in total sterol transport from the PM to the ER in temperature-sensitive mutant yeast strains missing all seven Osh proteins.…”

Section: Er and Plasma Membranementioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

273

200

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The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.T he endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions, including the synthesis of proteins and lipids, and regulation of intracellular calcium levels. This review focuses on the distinct and complex morphology of the ER. The structure of the ER is complex because of the numerous distinct domains that exist within one continuous membrane bilayer. These domains are shaped by interactions with the cytoskeleton, by proteins that stabilize membrane shape, and by a homotypic fusion machinery that allows the ER membrane to maintain its continuity and identity. The ER also contains domains that contact the plasma membrane (PM) and other organelles including the Golgi, endosomes, mitochondria, lipid droplets, and peroxisomes. ER contact sites with other organelles and the PM are both abundant and dispersed throughout the cytoplasm, suggesting that they too could influence the overall architecture of the ER. As we will discuss here, ER shape and distribution are regulated by many intrinsic and extrinsic forces. ER STRUCTURE AND FORMATION Domains of the ER Are Stabilized by Membrane-Shaping ProteinsThe endoplasmic reticulum (ER) is a large membrane-bound compartment spread throughout the cytoplasm of eukaryotic cells. It is divided into three major morphologies that include the nuclear envelope (NE), peripheral ER cisternae, and an interconnected tubular network

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“…Osh proteins have previously been implicated in non-vesicular sterol trafficking between the ER and the PM, but recent work suggests an additional role of these proteins as phosphatidylinositol-4-phosphate (PI-4-P) sensors that modulate PI-4-P levels in the PM by regulating the ER-resident PI-4-P phosphatase Sac1 at the ER-PM contact sites (Stefan et al , 2011 ). A recent study of Drin, Antonny, and coworkers demonstrated that Osh4 binds sterols and PI-4-P in the same binding site and may, thus, generate a sterol gradient between the ER and the Golgi (de Saint -Jean et al, 2011 ). Such a behavior may apply to all sterol-binding proteins, which may use PIPs for their specific targeting and sterol delivery.…”

Section: Organellar Contact Zones As Novel Microcompartmentsmentioning

confidence: 99%

Cellular microcompartments constitute general suborganellar functional units in cells

Holthuis

Ungermann

2013

Biological Chemistry

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All cells are compartmentalized to facilitate enzymatic reactions or cellular dynamics. In eukaryotic cells, organelles differ in their protein/lipid repertoire, luminal ion composition, pH, and redox status. In addition, organelles contain specialized subcompartments even within the same membrane or within its lumen. Moreover, the bacterial plasma membrane reveals a remarkable degree of organization, which is recapitulated in eukaryotic cells and often linked to cell signaling. Finally, protein-based compartments are also known in the bacterial and eukaryotic cytosol. As the organizing principle of such cellular subcompartments is likely similar, previous definitions like rafts, microdomains, and all kinds of ' -somes ' fall short as a general denominator to describe such suborganellar structures. Within this review, we will introduce the term cellular microcompartment as a general suborganellar functional unit and discuss its relevance to understand subcellular organization and function.

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Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers

Abstract: The yeast Kes1p/Osh4p protein functions as a sterol/PI(4)P exchanger between lipid membranes, which suggests the possibility of creating a sterol gradient via phosphoinositide metabolism.

Cited by 342 publications

References 42 publications

Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

Cellular microcompartments constitute general suborganellar functional units in cells

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