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N-Glycans and Quality Control of Proteins

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Abstract

Glycosylation is one of the most ubiquitous posttranslational modifications for eukaryotic proteins. There are numerous examples of the attachment of glycans to carrier proteins resulting in changes in their physicochemical properties, such as solubility or heat stability, as well as physiological properties, such as bioactivity or intra- or intercellular trafficking. In addition, recent studies have revealed that N-glycans can act as a readout for the folding status of glycoproteins in the endoplasmic reticulum (ER), so that only proper amounts of functional proteins are made and delivered to their respective destinations. This process is often called the glycoprotein quality control system, as a part of the ER protein homeostasis machinery. After misfolded glycoproteins are targeted for destruction in the ER, they are eventually retrotranslocated into the cytosol for proteasomal degradation. In the cytosol, glycans are again used for recognition by ubiquitin ligases but are eventually removed from glycoproteins in order to efficiently degrade misfolded glycoproteins. In the present review, a particular focus will be on the mannose-trimming processes, whereby N-glycan-dependent ER-associated degradation signals are created and recognized in the ER, as well as on the function of Fbs proteins and PNGase that recognize N-glycans in the cytosol.

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Acknowledgement

We thank Dr. Akira Hosomi (Glycometabolome Team, RIKEN) for critically reading our manuscript.

Note Recently, it is reported that EDEM2 processes mannose from the middle (B) branch of N-glycans in the vertebrate ER (Ninagawa et al. 2014).

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Nobuko Hosokawa

  2. Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Tadashi Suzuki

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Correspondence to Nobuko Hosokawa .

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Editors and Affiliations

  1. Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Tadashi Suzuki

  2. Department of Analytical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Kazuaki Ohtsubo

  3. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Naoyuki Taniguchi

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Hosokawa, N., Suzuki, T. (2015). N-Glycans and Quality Control of Proteins. In: Suzuki, T., Ohtsubo, K., Taniguchi, N. (eds) Sugar Chains. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55381-6_1

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