Seminars in Cell & Developmental Biology 41 (2015) 70
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
Glycoprotein maturation and quality control
Sugar can make our coffee taste much better and when added onto nascent or still unfolded newly synthesized proteins, oligosaccharides can also make these vulnerable polypeptides more soluble in the crowded endoplasmic reticulum (ER) environment. Most importantly, oligosaccharides attached to proteins in the ER attract a set of sugar-binding proteins, or lectins, that act as molecular chaperones and sorting receptors. Lectin chaperones participate in functional complexes containing oxidoreductases or prolylisomerases that catalyze rate-limiting reaction of folding programs. Most proteins will attain the native structure and will be transported to their intra- or extracellular site of activity. However, despite all this assistance, protein folding may fail and misfolded proteins may remain trapped in the first station of the secretory pathway, the ER. Recognition of proteins that have a hard time attaining their native structure is a task for sugar modifying enzymes that mark unfolded or misfolded proteins for retention in the folding compartment. This retention mechanism is mediated by the so-called calnexin (and calreticulin) cycle where immature polypeptides spend a given amount of time (minutes to several hours) or revolution in a cycle that supports additional opportunity to reach their native and functional state. As time goes on, the protein-bound oligosaccharides become smaller and smaller by loosing, one glucose and mannose residues one after another. A dedicated set of yet another ER-resident lectin family, survey the
http://dx.doi.org/10.1016/j.semcdb.2015.05.009 1084-9521/© 2015 Published by Elsevier Ltd.
ER lumen in search of old glycoproteins that failed to leave the compartment before their oligosaccharides have lost their terminal mannoses. These old and aberrant structures are delivered to the ER membrane for dislocation into the cytoplasm by an obscure mechanism of translocation, and once they immerge into the cytoplasm residual sugars are removed, the polypeptide is then ubiquitinated and degraded by proteasomes. While much of what we know about glycoprotein quality control involves Asn or N-linked glycans, recent studies have found that O-linked glycans also play a role in glycoprotein quality control. Seven review articles describing these important steps in protein maturation and quality control can be found in this issue of Seminars in Cell and Developmental Biology. We wish to thank the authors for their informative contributions that summarize the latest details of these fascinating stories. Maurizio Molinari Institute for Research in Biomedicine Bellinzona, Switzerland Daniel N. Hebert University of Massachusetts, Amherst, MA, USA
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
Glycoprotein maturation and quality control
Sugar can make our coffee taste much better and when added onto nascent or still unfolded newly synthesized proteins, oligosaccharides can also make these vulnerable polypeptides more soluble in the crowded endoplasmic reticulum (ER) environment. Most importantly, oligosaccharides attached to proteins in the ER attract a set of sugar-binding proteins, or lectins, that act as molecular chaperones and sorting receptors. Lectin chaperones participate in functional complexes containing oxidoreductases or prolylisomerases that catalyze rate-limiting reaction of folding programs. Most proteins will attain the native structure and will be transported to their intra- or extracellular site of activity. However, despite all this assistance, protein folding may fail and misfolded proteins may remain trapped in the first station of the secretory pathway, the ER. Recognition of proteins that have a hard time attaining their native structure is a task for sugar modifying enzymes that mark unfolded or misfolded proteins for retention in the folding compartment. This retention mechanism is mediated by the so-called calnexin (and calreticulin) cycle where immature polypeptides spend a given amount of time (minutes to several hours) or revolution in a cycle that supports additional opportunity to reach their native and functional state. As time goes on, the protein-bound oligosaccharides become smaller and smaller by loosing, one glucose and mannose residues one after another. A dedicated set of yet another ER-resident lectin family, survey the
http://dx.doi.org/10.1016/j.semcdb.2015.05.009 1084-9521/© 2015 Published by Elsevier Ltd.
ER lumen in search of old glycoproteins that failed to leave the compartment before their oligosaccharides have lost their terminal mannoses. These old and aberrant structures are delivered to the ER membrane for dislocation into the cytoplasm by an obscure mechanism of translocation, and once they immerge into the cytoplasm residual sugars are removed, the polypeptide is then ubiquitinated and degraded by proteasomes. While much of what we know about glycoprotein quality control involves Asn or N-linked glycans, recent studies have found that O-linked glycans also play a role in glycoprotein quality control. Seven review articles describing these important steps in protein maturation and quality control can be found in this issue of Seminars in Cell and Developmental Biology. We wish to thank the authors for their informative contributions that summarize the latest details of these fascinating stories. Maurizio Molinari Institute for Research in Biomedicine Bellinzona, Switzerland Daniel N. Hebert University of Massachusetts, Amherst, MA, USA
