Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance

Kailash Gulshan; Puja Shahi; W Scott Moye-Rowley

doi:10.1091/mbc.E09-06-0519

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Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance

Journal article

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Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance

Kailash Gulshan, Puja Shahi and W Scott Moye-Rowley

Molecular biology of the cell, Vol.21(3), pp.443-455

02/01/2010

DOI: 10.1091/mbc.E09-06-0519

PMCID: PMC2814789

PMID: 20016005

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Abstract

Control of lipid composition of membranes is crucial to ensure normal cellular functions. Saccharomyces cerevisiae has two different phosphatidylserine decarboxylase enzymes (Psd1 and Psd2) that catalyze formation of phosphatidylethanolamine. The mitochondrial Psd1 provides roughly 70% of the phosphatidylethanolamine (PE) biosynthesis in the cell with Psd2 carrying out the remainder. Here, we demonstrate that loss of Psd2 causes cells to acquire sensitivity to cadmium even though Psd1 remains intact. This cadmium sensitivity results from loss of normal activity of a vacuolar ATP-binding cassette transporter protein called Ycf1. Measurement of phospholipid levels indicates that loss of Psd2 causes a specific reduction in vacuolar membrane PE levels, whereas total PE levels are not significantly affected. The presence of a phosphatidylinositol transfer protein called Pdr17 is required for Psd2 function and normal cadmium tolerance. We demonstrate that Pdr17 and Psd2 form a complex in vivo that seems essential for maintenance of vacuolar PE levels. Finally, we refine the localization of Psd2 to the endosome arguing that this enzyme controls vacuolar membrane phospholipid content by regulating phospholipids in compartments that will eventually give rise to the vacuole. Disturbance of this regulation of intracellular phospholipid balance leads to selective loss of membrane protein function in the vacuole.

ATP-Binding Cassette Transporters - genetics

ATP-Binding Cassette Transporters - metabolism

Cadmium - metabolism

Carboxy-Lyases - genetics

Carboxy-Lyases - metabolism

Cell Membrane - chemistry

Cell Membrane - metabolism

Endosomes - metabolism

Endosomes - ultrastructure

Isoenzymes - genetics

Isoenzymes - metabolism

Membrane Lipids - metabolism

Mitochondria - metabolism

Phosphatidylethanolamines - biosynthesis

Phospholipid Transfer Proteins - genetics

Phospholipid Transfer Proteins - metabolism

R-SNARE Proteins - genetics

R-SNARE Proteins - metabolism

Recombinant Fusion Proteins - genetics

Recombinant Fusion Proteins - metabolism

Saccharomyces cerevisiae - cytology

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae - metabolism

Saccharomyces cerevisiae Proteins - genetics

Saccharomyces cerevisiae Proteins - metabolism

Vacuoles - metabolism

Vacuoles - ultrastructure

Details

Title: Subtitle: Compartment-specific synthesis of phosphatidylethanolamine is required for normal heavy metal resistance
Creators: Kailash Gulshan - University of Iowa
Puja Shahi - University of Iowa
W Scott Moye-Rowley - University of Iowa
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.21(3), pp.443-455
DOI: 10.1091/mbc.E09-06-0519
PMID: 20016005
PMCID: PMC2814789
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: R01 GM049825 / NIGMS NIH HHS R01 GM075120 / NIGMS NIH HHS GM-75120 / NIGMS NIH HHS
Language: English
Date published: 02/01/2010
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984297607602771

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