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Papers In Press, published online ahead of print November 3, 2000
J. Biol. Chem, 10.1074/jbc.C000710200
Submitted on October 9, 2000
Revised on November 3, 2000
Accepted on November 3, 2000

Mutations in yeast ARV1 alter intracellular sterol distribution and are complemented by human ARV1

Arthur H Tinkelenberg, Ying Liu, Frederick Alcantara, Sohail Khan, Zhongmin Guo, Martin Bard, and Stephen L. Sturley

Institute of Human Nutrition, Columbia University, New York, NY 10032

Corresponding Author: sls37{at}columbia.edu

Intracellular cholesterol redistribution between membranes and its subsequent esterification are critical aspects of lipid homeostasis that prevent free sterol toxicity. To identify genes that mediate sterol trafficking, we screened for yeast mutants that were inviable in the absence of sterol esterification. Mutations in the novel gene, ARV1, render cells dependent on sterol esterification for growth, nystatin sensitive, temperature sensitive, and anaerobically inviable. Cells lacking Arv1p display altered intracellular sterol distribution and are defective in sterol uptake, consistent with a role for Arv1p in trafficking sterol into the plasma membrane. Human ARV1, a predicted sequence ortholog of yeast ARV1, complements the defects associated with deletion of the yeast gene. The genes are predicted to encode transmembrane proteins with potential zinc binding motifs. We propose that ARV1 is a novel mediator of eukaryotic sterol homeostasis.


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