Journal
TRENDS IN BIOCHEMICAL SCIENCES
Volume 37, Issue 10, Pages 404-410Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibs.2012.07.005
Keywords
secretory pathway; carbohydrates; endoplasmic reticulum
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Funding
- US Public Health [GM086874, GM094848]
- Foundation for Research on Neurodegenerative Diseases
- Fondazione San Salvatore
- Swiss National Science Foundation
- Association Francaise contre les Myopathies
- Novartis Stiftung fur medizinisch-biologische Forschung
- Gabriele Foundation
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Nascent polypeptides entering the endoplasmic reticulum (ER) are covalently modified with pre-assembled oligosaccharides. The terminal glucose and mannose residues are immediately removed after transfer of the oligosaccharide onto newly synthesized polypeptides. This processing determines whether the polypeptide will be retained in the ER, transported along the secretory pathway, or dislocated across the ER membrane for destruction. New avenues of research and some issues of controversy have recently been opened by the discovery that lectin oligosaccharide interactions stabilize supramolecular complexes between regulators of ER-associated degradation (ERAD). In this Opinion article, we propose a unified model that depicts carbohydrates acting both as flags signaling the fitness of a maturing protein and as docking sites that regulate the assembly and stability of the ERAD machinery.
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