The Conserved Oligomeric Golgi (COG) Complex Is Required for Normal Import of Fatty Acids in Saccharomyces Cerevisiae

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2004-08-19

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The goal of my work was to elucidate aspects of the mechanism of trafficking of membrane proteins to peroxisomes. The work described in this document centers around one protein from Saccharomyces cerevisiae, Cog7p. Cog7p is part of the conserved oligomeric Golgi (COG) complex. Results describing a basic function of Cog7p were published well after I began studying this protein. Nevertheless, I use the nomenclature outlined in that work. Cog7p functions in intra-Golgi vesicular transport in concert with seven other proteins. This protein complex is found in both yeast and mammals. We found Cog7p in a different context through a screen to identify proteins that function in the trafficking of membrane proteins to peroxisomes. In the screen a portion of Cog7p was found to interact with the membrane peroxisomal targeting sequence, mPTS, of the Candida boidinii peroxisomal membrane protein, Pmp47. I studied peroxisomal biogenesis in a strain of Saccharomyces cerevisiae in which the COG7 gene had been deleted. I showed that Cog7p was not required for peroxisomal biogenesis, but in so doing, established that Cog7p was required for the proper metabolism of fatty acids in a peroxisome-independent manner. I showed that Cog7p was required for the normal import of fatty acids; without Cog7p, yeast cells imported abnormally high amounts of free fatty acid from the environment. My results are consistent with the hypothesis that one or more protein(s) involved in fatty acid import require the COG complex for proper processing. My work ends before such a protein was identified, but I provide leads that if pursued would contribute to understanding the regulation of fatty acid import into yeast cells.

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