Two distinct proteolytic systems responsible for glucose-induced degradation of fructose-1,6-bisphosphatase and the Gal2p transporter in the yeast Saccharomyces cerevisiae share the same protein components of the glucose signaling pathway.
Addition of glucose to Saccharomyces cerevisiae inactivates the galactose transporter Gal2p and fructose-1,6-bisphosphatase (FBPase) by a mechanism called glucose- or catabolite-induced inactivation, which ultimately results in a degradation of both proteins. It is well established, however, that glucose induces internalization of Gal2p into the endocytotic pathway and its subsequent proteolysis in the vacuole, whereas FBPase is targeted to the 26 S proteasome for proteolysis under similar inactivation conditions. Here we report that two distinct proteolytic systems responsible for specific degradation of two conditionally short-lived protein targets, Gal2p and FBPase, utilize most (if not all) protein components of the same glucose sensing (signaling) pathway. Indeed, initiation of Gal2p and FBPase proteolysis appears to require rapid transport of those substrates of the Hxt transporters that are at least partially metabolized by hexokinase Hxk2p. Also, maltose transported via the maltose-specific transporter(s) generates an appropriate signal that culminates in the degradation of both proteins. In addition, Grr1p and Reg1p were found to play a role in transduction of the glucose signal for glucose-induced proteolysis of Gal2p and FBPase. Thus, one signaling pathway initiates two different proteolytic mechanisms of catabolite degradation, proteasomal proteolysis and endocytosis followed by lysosomal proteolysis.
Horak
Jaroslav
J
Institute of Physiology, Department of Membrane Transport, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
Regelmann
Jochen
J
Wolf
Dieter H
DH
D015153:Blotting, Western; D004705:Endocytosis; D005632:Fructose / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000737:chemistry* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D008320:Maltose / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013997:Time Factors
C106901:GAL2 protein, S cerevisiae; D009004:Monosaccharide Transport Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D005632:Fructose; D008320:Maltose; D006593:Hexokinase; D006597:Fructose-Bisphosphatase; D005947:Glucose