The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation.
Asn-linked glycans (N-glycans) play important roles in the quality control (QC) of glycoprotein folding in the endoplasmic reticulum (ER) lumen and in ER-associated degradation (ERAD) of proteins by cytosolic proteasomes. A UDP-Glc:glycoprotein glucosyltransferase glucosylates N-glycans of misfolded proteins, which are then bound and refolded by calreticulin and/or calnexin in association with a protein disulfide isomerase. Alternatively, an alpha-1,2-mannosidase (Mns1) and mannosidase-like proteins (ER degradation-enhancing alpha-mannosidase-like proteins 1, 2, and 3) are part of a process that results in the dislocation of misfolded glycoproteins into the cytosol, where proteins are degraded in the proteasome. Recently we found that numerous protists and fungi contain 0-11 sugars in their N-glycan precursors versus 14 sugars in those of animals, plants, fungi, and Dictyostelium. Our goal here was to determine what effect N-glycan precursor diversity has on N-glycan-dependent QC systems of glycoprotein folding and ERAD. N-glycan-dependent QC of folding (UDP-Glc:glycoprotein glucosyltransferase, calreticulin, and/or calnexin) was present and active in some but not all protists containing at least five mannose residues in their N-glycans and was absent in protists lacking Man. In contrast, N-glycan-dependent ERAD appeared to be absent from the majority of protists. However, Trypanosoma and Trichomonas genomes predicted ER degradation-enhancing alpha-mannosidase-like protein and Mns1 orthologs, respectively, each of which had alpha-mannosidase activity in vitro. Phylogenetic analyses suggested that the diversity of N-glycan-dependent QC of glycoprotein folding (and possibly that of ERAD) was best explained by secondary loss. We conclude that N-glycan precursor length has profound effects on N-glycan-dependent QC of glycoprotein folding and ERAD.
Banerjee
Sulagna
S
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA 02118, USA.
Vishwanath
Prashanth
P
Cui
Jike
J
Kelleher
Daniel J
DJ
Gilmore
Reid
R
Robbins
Phillips W
PW
Samuelson
John
J
D000818:Animals; D002240:Carbohydrate Sequence; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D004748:Entamoeba histolytica / Q000201:enzymology / Q000378:metabolism; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000378:metabolism*; D008361:Mannosidases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology / Q000378:metabolism; D011134:Polysaccharides / Q000502:physiology*; D011237:Predictive Value of Tests; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014244:Trichomonas / Q000201:enzymology / Q000378:metabolism
D006023:Glycoproteins; D011134:Polysaccharides; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase; D046988:Proteasome Endopeptidase Complex