000070972 001__ 70972
000070972 005__ 20200117211602.0
000070972 0247_ $$2doi$$a10.1074/jbc.M117.817981
000070972 0248_ $$2sideral$$a106635
000070972 037__ $$aART-2018-106635
000070972 041__ $$aeng
000070972 100__ $$aWang, S.
000070972 245__ $$aSite-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions
000070972 260__ $$c2018
000070972 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070972 5203_ $$aThe low-density lipoprotein receptor (LDLR) and related receptors are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O-glycan sites. Moreover, we found that O-glycan modifications at these sites are selectively controlled by the GalNAc-transferase isoform, GalNAc-T11. However, the effects of GalNAc-T11–mediated O-glycosylation on LDLR and related receptor localization and function are unknown. Here, we characterized O-glycosylation of LDLR-related proteins and identified conserved O-glycosylation sites in the LA linker regions of VLDLR, LRP1, and LRP2 (Megalin) from both cell lines and rat organs. Using a panel of gene-edited isogenic cell line models, we demonstrate that GalNAc-T11–mediated LDLR and VLDLR O-glycosylation is not required for transport and cell-surface expression and stability of these receptors but markedly enhances LDL and VLDL binding and uptake. Direct ELISA-based binding assays with truncated LDLR constructs revealed that O-glycosylation increased affinity for LDL by 5-fold. The molecular basis for this observation is currently unknown, but these findings open up new avenues for exploring the roles of LDLR-related proteins in disease.
000070972 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000070972 592__ $$a2.403$$b2018
000070972 593__ $$aBiochemistry$$c2018$$dQ1
000070972 593__ $$aMolecular Biology$$c2018$$dQ1
000070972 593__ $$aCell Biology$$c2018$$dQ1
000070972 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070972 700__ $$aMao, Y.
000070972 700__ $$aNarimatsu, Y.
000070972 700__ $$aYe, Z.
000070972 700__ $$aTian, W.
000070972 700__ $$aGoth, C.K.
000070972 700__ $$aLira-Navarrete, E.
000070972 700__ $$aPedersen, N.B.
000070972 700__ $$aBenito-Vicente, A.
000070972 700__ $$aMartin, C.
000070972 700__ $$aUribe, K.B.
000070972 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R.$$uUniversidad de Zaragoza
000070972 700__ $$aChristoffersen, C.
000070972 700__ $$aSeidah, N.G.
000070972 700__ $$aNielsen, R.
000070972 700__ $$aChristensen, E.I.
000070972 700__ $$aHansen, L.
000070972 700__ $$aBennett, E.P.
000070972 700__ $$aVakhrushev, S.Y.
000070972 700__ $$aSchjoldager, K.T.
000070972 700__ $$aClausen, H.
000070972 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000070972 773__ $$g293, 19 (2018), 7408-7422$$pJ. biol. chem.$$tJournal of Biological Chemistry$$x0021-9258
000070972 8564_ $$s511943$$uhttps://zaguan.unizar.es/record/70972/files/texto_completo.pdf$$yVersión publicada
000070972 8564_ $$s149625$$uhttps://zaguan.unizar.es/record/70972/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070972 909CO $$ooai:zaguan.unizar.es:70972$$particulos$$pdriver
000070972 951__ $$a2020-01-17-21:13:04
000070972 980__ $$aARTICLE