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Gewählte Publikation:

Hüttner, S; Veit, C; Vavra, U; Schoberer, J; Dicker, M; Maresch, D; Altmann, F; Strasser, R; .
(2014): A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation.
Biochem J. 2014; 464(3):401-411 FullText FullText_BOKU

Abstract:
N-glycosylation of proteins plays an important role in the determination of the fate of newly synthesized glycoproteins in the endoplasmic reticulum (ER). Specific oligosaccharide structures recruit molecular chaperones that promote folding or mannosebinding lectins that assist in the clearance of improperly-folded glycoproteins by delivery to ER-associated degradation (ERAD). In plants, the mechanisms and factors that recognize non-native proteins and sort them to ERAD are poorly understood. In the present study, we provide evidence that a misfolded variant of the STRUBBELIG (SUB) extracellular domain (SUBEX-C57Y) is degraded in a glycan-dependent manner in plants. SUBEX-C57Y is an ER-retained glycoprotein with three N-glycans that is stabilized in the presence of kifunensine, a potent inhibitor of alpha-mannosidases. Stable expression in Arabidopsis thaliana knockout mutants revealed that SUBEX-C57Y degradation is dependent on the ER lectin OS9 and its associated ERAD factor SEL1L. SUBEX-C57Y was also stabilized in plants lacking the alpha-mannosidases MNS4 and MNS5 that generate a terminal alpha 1,6-linked mannose on the C-branch of N-glycans. Notably, the glycan signal for degradation is not constrained to a specific position within SUBEX-C57Y. Structural analysis revealed that SUBEX-C57Y harbours considerable amounts of Glc(1)Man(7)GlcNAc(2) N-glycans suggesting that the ER-quality control processes involving calnexin/calreticulin (CNX/CRT) and BRAD are tightly interconnected to promote protein folding or disposal by termination of futile folding attempts.
Autor*innen der BOKU Wien:
Altmann Friedrich
Maresch Daniel
Schoberer Jennifer
Strasser Richard
Vavra Ulrike
Veit Christiane

Find related publications in this database (Keywords)
cell biology
endoplasmic reticulum
endoplasmic-reticulum-associated degradation (ERAD)
glycobiology
glycoprotein
glycosylation
protein degradation
protein misfolding


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