Compartment-specific Synthesis of Phosphatidylethanolamine Is Required for Normal Heavy Metal Resistance

Gulshan, Kailash; Shahi, Puja; Moye‐Rowley, W. Scott

doi:10.1091/mbc.e09-06-0519

Cited by 70 publications

(87 citation statements)

References 78 publications

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“…This result indicates that the Psd2-NTRD is sufficient for promoting the interaction with PstB2p and that the catalytic domain is dispensable for this presumably transportrelated function. During the course of this work, several other reports (10,24,25) have appeared demonstrating the existence of an interaction between Psd2p and PstB2p. Our study thus adds additional independent evidence regarding the protein domains involved in facilitating this interaction and further supports the existence and functional importance of this complex.…”

Section: Recombinant Pstb2pmentioning

confidence: 74%

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Riekhof

Jones

et al. 2014

Journal of Biological Chemistry

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Background:The machinery for interorganelle phosphatidylserine (PtdSer) transport is poorly defined at the molecular level. Results: Molecular interaction studies identify specific protein-protein and protein-lipid interactions in PtdSer transport. Conclusion: A protein and lipid interaction network defines key participants in PS transport to the locus of PtdSer-decarboxylase 2. Significance: This study identifies important molecular participants involved in non-vesicular phospholipid traffic.

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Section: Recombinant Pstb2pmentioning

confidence: 74%

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Riekhof

Jones

et al. 2014

Journal of Biological Chemistry

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“…ScYor1 is the only known ABCC class transporter in this yeast that is localized to the plasma membrane (33). The other ABCC transporters are found in the vacuolar membrane (34,35). A BLAST search using the ScYor1 protein sequence identified 10 ABCC class transporters in A. fumigatus but, interestingly, only a single protein that shared the unique structure of ScYor1.…”

Section: Resultsmentioning

confidence: 99%

Contributions of Aspergillus fumigatus ATP-Binding Cassette Transporter Proteins to Drug Resistance and Virulence

2013

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In yeast cells such as those of Saccharomyces cerevisiae, expression of ATP-binding cassette (ABC) transporter proteins has been found to be increased and correlates with a concomitant elevation in azole drug resistance. In this study, we investigated the roles of two Aspergillus fumigatus proteins that share high sequence similarity with S. cerevisiae Pdr5, an ABC transporter protein that is commonly overproduced in azole-resistant isolates in this yeast. The two A. fumigatus genes encoding the ABC transporters sharing the highest sequence similarity to S. cerevisiae Pdr5 are called abcA and abcB here. We constructed deletion alleles of these two different ABC transporter-encoding genes in three different strains of A. fumigatus. Loss of abcB invariably elicited increased azole susceptibility, while abcA disruption alleles had variable phenotypes. Specific antibodies were raised to both AbcA and AbcB proteins. These antisera allowed detection of AbcB in wild-type cells, while AbcA could be visualized only when overproduced from the hspA promoter in A. fumigatus. Overproduction of AbcA also yielded increased azole resistance. Green fluorescent protein fusions were used to provide evidence that both AbcA and AbcB are localized to the plasma membrane in A. fumigatus. Promoter fusions to firefly luciferase suggested that expression of both ABC transporter-encoding genes is inducible by azole challenge. Virulence assays implicated AbcB as a possible factor required for normal pathogenesis. This work provides important new insights into the physiological roles of ABC transporters in this major fungal pathogen.

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“…For example, the activity of the yeast cytochrome bc 1 complex requires cardiolipin, and specific lipid-binding sites have been identified in x-ray structures of the protein complex (41,42). Changes in phosphoethanolamine levels have recently been shown to affect the activity of the vacuolar membrane-localized ABC transporter Ycf1 (43). Similarly, Aus1 activity may be regulated by the PS levels in the cell.…”

Section: Discussionmentioning

confidence: 99%

The Yeast Plasma Membrane ATP Binding Cassette (ABC) Transporter Aus1

Marek

Milles

Schreiber

et al. 2011

Journal of Biological Chemistry

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The ATP binding cassette (ABC) transporter Aus1 is expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and is required for sterol uptake. These observations suggest that Aus1 promotes the translocation of sterols across membranes, but the precise transport mechanism has yet to be identified. In this study, an extraction and purification procedure was developed to characterize the Aus1 transporter. The detergent-solubilized protein was able to bind and hydrolyze ATP. Mutagenesis of the conserved lysine to methionine in the Walker A motif abolished ATP hydrolysis. Likewise, ATP hydrolysis was inhibited by classical inhibitors of ABC transporters. Upon reconstitution into proteoliposomes, the ATPase activity of Aus1 was specifically stimulated by phosphatidylserine (PS) in a stereoselective manner. We also found that Aus1-dependent sterol uptake, but not Aus1 expression and trafficking to the plasma membrane, was affected by changes in cellular PS levels. These results suggest a direct interaction between Aus1 and PS that is critical for the activity of the transporter.

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Compartment-specific Synthesis of Phosphatidylethanolamine Is Required for Normal Heavy Metal Resistance

Cited by 70 publications

References 78 publications

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Contributions of Aspergillus fumigatus ATP-Binding Cassette Transporter Proteins to Drug Resistance and Virulence

The Yeast Plasma Membrane ATP Binding Cassette (ABC) Transporter Aus1

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