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A more recent version of this article appeared on July 1, 2002
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Submitted on November 30, 2001
Revised on March 19, 2002
Accepted on March 29, 2002
1 Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA
2 Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA
3 Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia Canada, B3H 4H7
4 Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia Canada, B3H 4H7
5 Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia Canada, B3H 4H7
6 Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA
* Corresponding author. E-mail address: bktis{at}med.unc.edu.
Yeast phosphatidylinositol transfer protein (Sec14p) coordinates lipid metabolism with protein trafficking events. This essential Sec14p requirement for Golgi function is bypassed by mutations in any one of seven genes that control phosphatidylcholine or phosphoinositide metabolism. In addition to these 'bypass Sec14p' mutations, Sec14p-independent Golgi function requires phospholipase D (PLD) activity. The identities of lipids that mediate Sec14p-dependent Golgi function, and the identity of the proteins that respond to Sec14p-mediated regulation of lipid metabolism, remain elusive. We now report genetic evidence to suggest that two ARF-GTPase activating proteins (ARFGAPs), Gcs1p and Age2p, may represent these lipid responsive elements, and that Gcs1p/Age2p act downstream of Sec14p and PLD in both Sec14p-dependent and Sec14p-independent pathways for yeast Golgi function. In support, biochemical data indicate that Gcs1p and Age2p ARFGAP activities are both modulated by lipids implicated in regulation of Sec14p pathway function. These results suggest ARFGAPs are stimulatory factors required for regulation of Golgi function by the Sec14p pathway, and that Sec14p-mediated regulation of lipid metabolism interfaces with the activity of proteins involved in control of the ARF cycle.
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