Allele-specific suppression of a defective brassinosteroid receptor reveals a physiological role of UGGT in ER quality control.
UDP-glucose:glycoprotein glucosyltransferase (UGGT) is a presumed folding sensor of protein quality control in the endoplasmic reticulum (ER). Previous biochemical studies with nonphysiological substrates revealed that UGGT can glucosylate nonnative glycoproteins by recognizing subtle folding defects; however, its physiological function remains undefined. Here, we show that mutations in the Arabidopsis EBS1 gene suppressed the growth defects of a brassinosteroid (BR) receptor mutant, bri1-9, in an allele-specific manner by restoring its BR sensitivity. Using a map-based cloning strategy, we discovered that EBS1 encodes the Arabidopsis homolog of UGGT. We demonstrated that bri1-9 is retained in the ER through interactions with several ER chaperones and that ebs1 mutations significantly reduce the stringency of the retention-based ER quality control, allowing export of the structurally imperfect yet biochemically competent bri1-9 to the cell surface for BR perception. Thus, our discovery provides genetic support for a physiological role of UGGT in high-fidelity ER quality control.
Jin
Hua
H
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Yan
Zhenyan
Z
Nam
Kyoung Hee
KH
Li
Jianming
J
D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*
D029681:Arabidopsis Proteins; C478974:EBS protein, Arabidopsis; D018398:Homeodomain Proteins; D005964:Glucosyltransferases; C072423:mannosylglycoprotein 1,3-glucosyltransferase; D011494:Protein Kinases; C108270:BRI1 protein, Arabidopsis