Ypk1, the yeast orthologue of the human serum- and glucocorticoid-induced kinase, is required for efficient uptake of fatty acids.
Fatty acids constitute an important energy source for various tissues. The mechanisms that mediate and control uptake of free fatty acids from the circulation, however, are poorly understood. Here we show that efficient fatty-acid uptake by yeast cells requires the protein kinase Ypk1, the orthologue of the human serum- and glucocorticoid-induced kinase Sgk1. ypk1Delta mutant cells fail to grow under conditions that render cells auxotrophic for fatty acids, show a reduced uptake of radiolabelled or fluorescently labelled fatty acids, lack the facilitated component of the uptake activity, and have elevated levels of fatty acids in a bovine serum albumin (BSA) back-extractable compartment. Efficient fatty-acid uptake and/or incorporation requires the protein-kinase activity of Ypk1, because a kinase-dead point-mutant allele of YPK1 is defective in this process. This function of Ypk1 in fatty-acid uptake and/or incorporation is functionally conserved, because expression of the human Sgk1 kinase rescues ypk1Delta mutant yeast. These observations suggest that Ypk1 and possibly the human Sgk1 kinase affect fatty-acid uptake and thus energy homeostasis through regulating endocytosis. Consistent with such a proposition, mutations that block early steps of endocytosis display reduced levels of fatty-acid uptake.
Jacquier
Nicolas
N
Department of Medicine, Division of Biochemistry, University of Fribourg, Chemin du Musee 5, 1700 Fribourg, Switzerland.
Schneiter
Roger
R
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
D005227:Fatty Acids; D038362:Glycogen Synthase Kinase 3; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D012710:Serum Albumin, Bovine; D000099184:Serum-Glucocorticoid Regulated Kinases; C068124:MCK1 protein, S cerevisiae