Phospholipid Flippases

Daleke, David L.

doi:10.1074/jbc.r600035200

Cited by 231 publications

(192 citation statements)

References 72 publications

Supporting

Mentioning

189

Contrasting

Unclassified

Order By: Relevance

“…EPT is an integral membrane protein with seven predicted transmembrane domains (78,80,81) and is found predominantly in the ER, with some other reports of nuclear envelope localization, whereas CPT has been observed in the Golgi (14). It has been demonstrated that the EPT active site faces the cytoplasm and therefore the biosynthesis of PE occurs asymmetrically on the cytoplasmic surface of the ER (82,83). C/EPT sequences contain the CDP-alcohol phosphatidyltransferase motif DG(X) 2 AR(X) 8 G(X) 3 D(X) 3 D, which is also present in CPTs, C/EPTs, phosphatidylinositol synthases, cardolipin synthases, and phosphatidylglycerol phosphate synthases.…”

Section: The Ctp:phosphocholine Cytidylyltransferasementioning

confidence: 99%

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

View full text Add to dashboard Cite

SummaryThe glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases. IUBMBIUBMB Life, 62(6): [414][415][416][417][418][419][420][421][422][423][424][425][426][427][428] 2010

show abstract

Section: The Ctp:phosphocholine Cytidylyltransferasementioning

confidence: 99%

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

View full text Add to dashboard Cite

show abstract

“…In this phospholipid asymmetry, phosphatidylcholine (PC) 2 is predominantly distributed in the outer leaflet facing extracellular space (exoplasmic leaflet), whereas phosphatidylethanolamine (PE) and phosphatidylserine (PS) are distributed in the inner leaflet facing the cytoplasm (cytoplasmic leaflet). The type 4 subfamily of P-type ATPase (P4-ATPase) seems to play an essential role to generate, maintain, and regulate phospholipid asymmetry by working as a "flippase," which translocates aminophospholipids from the exoplasmic leaflet to the cytoplasmic one in an energy-dependent manner (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Phospholipid Flippases Lem3p-Dnf1p and Lem3p-Dnf2p Are Involved in the Sorting of the Tryptophan Permease Tat2p in Yeast

Hachiro

Yamamoto

Nakano

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Lem3p-Dnf1p and Lem3p-Dnf2p are phospholipid flippases that generate phospholipid asymmetry in yeast. Results:The tryptophan permease Tat2p is missorted from the trans-Golgi network to the vacuole in the lem3⌬ mutant. Conclusion: Phospholipid asymmetry supports plasma membrane transport of Tat2p by inhibiting its improper ubiquitination at the trans-Golgi network. Significance: Phospholipid asymmetry may be involved in proper sorting of membrane proteins.

show abstract

“…Many of these proteins appear to indirectly regulate/alter cholesterol flux between the PM and HDL by acting as phospholipid flippases (e.g. ABCA1, P-gp) (21,24,28,29). Photocrosslinking and immunoprecipitation studies show that: (i) caveolin-1 (30,31), but not ABCA1 (24) or SRB1 (14), directly binds cholesterol; (ii) ABCA1 and SRB1, but not caveolin-1, directly bind HDL (21,22); (iii) While neither ABCA1, P-gp, or SRB1 contain a caveolin-1 'scaffold binding domain', ABCA1 may interact directly with caveolin-1 (22).…”

mentioning

confidence: 99%

A New N-Terminal Recognition Domain in Caveolin-1 Interacts with Sterol Carrier Protein-2 (SCP-2)

et al. 2007

View full text Add to dashboard Cite

Although plasma membrane domains such as caveolae provide an organizing principle for signaling pathways and cholesterol homeostasis in the cell, relatively little is known regarding specific mechanisms whereby intracellular lipid binding proteins are targeted to caveolae. Therefore, the interaction between caveolin-1 and sterol carrier protein-2 (SCP-2), a protein that binds and transfers both cholesterol and signaling lipids (e.g. phosphatidylinositides, sphingolipids), was examined by yeast two-hybrid, in vitro binding, and fluorescence resonance energy transfer analyses (FRET). Results of the in vivo and in vitro assays identified for the first time the N-terminal aa1-32 amphipathic α-helix of SCP-2 functionally interacted with caveolin-1. This interaction was independent of the classic caveolin-1 scaffolding domain in which many signaling proteins interact. Instead, SCP-2 bound caveolin-1 through a new domain identified in the N-terminal domain of caveolin-1 between amino acids 32-55. Modeling studies suggested that electrostatic interactions between the SCP-2 N-terminal aa1-32 amphipathic α-helical domain (cationic, positively charged face) and the caveolin-1 N-terminal aa33-59 α-helix (anionic, negatively charged face) may significantly contribute to this interaction. These findings provide new insights on how SCP-2 enhances cholesterol retention within the cell as well as regulates the distribution of signaling lipids such as phosphoinositides and sphingolipids at plasma membrane caveolae.Keywords sterol carrier protein-2; caveolae; caveolin-1; caveolae; cholesterol; signaling Increasing evidence indicates that cholesterol found at the cell surface plasma membrane (PM) is not randomly distributed, but instead organized into both transbilayer (1,2) and lateral (3,4) cholesterol-rich (and/or sphingolipid-rich) domains that adopt a unique, liquidordered structural organization (4-7). It has been postulated that this self-assembling property of cholesterol (and also sphingolipids) into domains in turn forms the structural basis for selective membrane protein organization (8). Support for this hypothesis is from numerous studies demonstrating that many PM proteins are functionally organized into lipid rafts and/or caveolae, a sub-fraction of lipid rafts that have proven to be a remarkably stable † Acknowledgments: This work was supported in part by the USPHS National Institutes of Health GM31651 (FS and AK) and GM62326 (JMB).

show abstract

Phospholipid Flippases

Cited by 231 publications

References 72 publications

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

Phospholipid Flippases Lem3p-Dnf1p and Lem3p-Dnf2p Are Involved in the Sorting of the Tryptophan Permease Tat2p in Yeast

A New N-Terminal Recognition Domain in Caveolin-1 Interacts with Sterol Carrier Protein-2 (SCP-2)

Contact Info

Product

Resources

About