{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:02:56Z","timestamp":1784224976521,"version":"3.55.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austria Science Fund","award":["P28218-B22"],"award-info":[{"award-number":["P28218-B22"]}]},{"name":"Austria Science Fund","award":["P31920-B32"],"award-info":[{"award-number":["P31920-B32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Endoplasmic reticulum (ER) quality control processes recognize and eliminate misfolded proteins to maintain cellular protein homeostasis and prevent the accumulation of defective proteins in the secretory pathway. Glycosylphosphatidylinositol (GPI)-anchored proteins carry a glycolipid modification, which provides an efficient ER export signal and potentially prevents the entry into ER-associated degradation (ERAD), which is one of the major pathways for clearance of terminally misfolded proteins from the ER. Here, we analyzed the degradation routes of different misfolded glycoproteins carrying a C-terminal GPI-attachment signal peptide in Arabidopsis thaliana. We found that a fusion protein consisting of the misfolded extracellular domain from Arabidopsis STRUBBELIG and the GPI-anchor attachment sequence of COBRA1 was efficiently targeted to hydroxymethylglutaryl reductase degradation protein 1 complex-mediated ERAD without the detectable attachment of a GPI anchor. Non-native variants of the GPI-anchored lipid transfer protein 1 (LTPG1) that lack a severely misfolded domain, on the other hand, are modified with a GPI anchor and targeted to the vacuole for degradation. Impaired processing of the GPI-anchoring signal peptide by mutation of the cleavage site or in a GPI-transamidase-compromised mutant caused ER retention and routed the non-native LTPG1 to ERAD. Collectively, these results indicate that for severely misfolded proteins, ER quality control processes are dominant over ER export. For less severely misfolded proteins, the GPI anchor provides an efficient ER export signal resulting in transport to the vacuole.<\/jats:p>","DOI":"10.1093\/plphys\/kiab181","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T19:56:12Z","timestamp":1619553372000},"page":"1878-1892","source":"Crossref","is-referenced-by-count":10,"title":["Proper protein folding in the endoplasmic reticulum is required for attachment of a glycosylphosphatidylinositol anchor in plants"],"prefix":"10.1093","volume":"186","author":[{"given":"Yun-Ji","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Vavra","sequence":"additional","affiliation":[{"name":"Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-6530","authenticated-orcid":false,"given":"Richard","family":"Strasser","sequence":"additional","affiliation":[{"name":"Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"2021080320323294400_kiab181-B1","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1091\/mbc.e08-01-0087","article-title":"Retrotranslocation of prion proteins from the endoplasmic reticulum by preventing GPI signal transamidation","volume":"19","author":"Ashok","year":"2008","journal-title":"Mol Biol Cell"},{"key":"2021080320323294400_kiab181-B2","doi-asserted-by":"crossref","first-page":"e1000479","DOI":"10.1371\/journal.ppat.1000479","article-title":"Selective processing and metabolism of disease-causing mutant prion proteins","volume":"5","author":"Ashok","year":"2009","journal-title":"PLoS Pathog"},{"key":"2021080320323294400_kiab181-B3","doi-asserted-by":"crossref","first-page":"611188","DOI":"10.3389\/fpls.2020.611188","article-title":"GPI-anchor synthesis in plants -a glycobiology perspective","volume":"11","author":"Beihammer","year":"2020","journal-title":"Front Plant Sci"},{"key":"2021080320323294400_kiab181-B4","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1104\/pp.20.00880","article-title":"p24 family proteins are involved in transport to the plasma membrane of GPI-anchored proteins in plants","volume":"184","author":"Bernat-Silvestre","year":"2020","journal-title":"Plant Physiol"},{"key":"2021080320323294400_kiab181-B5","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/S0021-9258(19)69848-0","article-title":"Phase separation of integral membrane proteins in Triton X-114 solution","volume":"256","author":"Bordier","year":"1981","journal-title":"J Biol Chem"},{"key":"2021080320323294400_kiab181-B6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1104\/pp.103.021170","article-title":"Identification of glycosylphosphatidylinositol-anchored proteins in Arabidopsis. A proteomic and genomic analysis","volume":"132","author":"Borner","year":"2003","journal-title":"Plant Physiol"},{"key":"2021080320323294400_kiab181-B7","doi-asserted-by":"crossref","first-page":"a013201","DOI":"10.1101\/cshperspect.a013201","article-title":"Protein folding in the endoplasmic reticulum","volume":"5","author":"Braakman","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2021080320323294400_kiab181-B8","first-page":"974","article-title":"A mutation in the catalytic subunit of the glycosylphosphatidylinositol transamidase disrupts growth, fertility, and stomata formation","volume":"171","author":"Bundy","year":"2016","journal-title":"Plant Physiol"},{"key":"2021080320323294400_kiab181-B9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/nph.16369","article-title":"Insights into endoplasmic reticulum-associated degradation in plants","volume":"226","author":"Chen","year":"2020","journal-title":"New Phytol"},{"key":"2021080320323294400_kiab181-B10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/0076-6879(95)50101-0","article-title":"Glycosylphosphatidylinositol-phospholipase D: a tool for glycosylphosphatidylinositol structural analysis","volume":"250","author":"Deeg","year":"1995","journal-title":"Methods Enzymol"},{"key":"2021080320323294400_kiab181-B11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00497-020-00395-9","article-title":"Bridging the GAPs in plant reproduction: a comparison of plant and animal GPI-anchored proteins","volume":"33","author":"Desnoyer","year":"2020","journal-title":"Plant Reprod"},{"key":"2021080320323294400_kiab181-B12","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1104\/pp.103.023580","article-title":"Glycosylphosphatidylinositol lipid anchoring of plant proteins. 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which is polarly localized and necessary for oriented cell expansion in Arabidopsis","volume":"15","author":"Schindelman","year":"2001","journal-title":"Genes Dev"},{"key":"2021080320323294400_kiab181-B37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1600-0854.2008.00841.x","article-title":"Arginine\/lysine residues in the cytoplasmic tail promote ER export of plant glycosylation enzymes","volume":"10","author":"Schoberer","year":"2009","journal-title":"Traffic"},{"key":"2021080320323294400_kiab181-B38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/pbi.12602","article-title":"Reduced paucimannosidic N-glycan formation by suppression of a specific \u03b2-hexosaminidase from Nicotiana benthamiana","volume":"15","author":"Shin","year":"2017","journal-title":"Plant Biotechnol J"},{"key":"2021080320323294400_kiab181-B39","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/tpj.13851","article-title":"The glycan-dependent ERAD machinery 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