Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast.
Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytoplasm and degraded by the proteasome. Processing intermediates of N-linked oligosaccharides on incompletely folded glycoproteins have an important role in their folding/refolding, and also in their targeting to proteolytic degradation. In Saccharomyces cerevisiae, we have identified a gene coding for a non-essential protein that is homologous to mannosidase I (HTM1) and that is required for degradation of glycoproteins. Deletion of the HTM1 gene does not affect oligosaccharide trimming. However, deletion of HTM1 does reduce the rate of degradation of the mutant glycoproteins such as carboxypeptidase Y, ABC-transporter Pdr5-26p and oligosaccharyltransferase subunit Stt3-7p, but not of mutant Sec61-2p, a non-glycoprotein. Our results indicate that although Htm1p is not involved in processing of N-linked oligosaccharides, it is required for their proteolytic degradation. We propose that this mannosidase homolog is a lectin that recognizes Man8GlcNAc2 oligosaccharides that serve as signals in the degradation pathway.
Jakob
C A
CA
Institute of Microbiology, ETH Zurich, Schmelzbergstrasse 7, CH-8092 Zurich, Switzerland. jacob@micro.biol.etz.ch
Bodmer
D
D
Spirig
U
U
Battig
P
P
Marcil
A
A
Dignard
D
D
Bergeron
J J
JJ
Thomas
D Y
DY
Aebi
M
M
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002236:Carbohydrate Conformation; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism; D043402:Cathepsin A; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006602:Hexosyltransferases; D006801:Humans; D015151:Immunoblotting; D008361:Mannosidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D014452:Ubiquitins / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D009844:Oligosaccharides; C092438:PDR5 protein, S cerevisiae; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D006602:Hexosyltransferases; C096554:STT3 protein, S cerevisiae; C434527:MNL1 protein, S cerevisiae; D008361:Mannosidases; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex