Allele-specific suppression of a defective brassinosteroid receptor reveals a physiological role of UGGT in ER quality control

Mol Cell. 2007 Jun 22;26(6):821-30. doi: 10.1016/j.molcel.2007.05.015.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arabidopsis / enzymology*
  • Arabidopsis / genetics
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum / genetics
  • Glucosyltransferases / genetics
  • Glucosyltransferases / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mutation*
  • Protein Kinases / deficiency
  • Protein Kinases / metabolism*

Substances

  • Arabidopsis Proteins
  • EBS protein, Arabidopsis
  • Homeodomain Proteins
  • Glucosyltransferases
  • mannosylglycoprotein 1,3-glucosyltransferase
  • Protein Kinases
  • BRI1 protein, Arabidopsis