1. Biochemistry and Chemical Biology
  2. Cell Biology

Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis

  1. Haik Mkhikian
  2. Christie-Lynn Mortales
  3. Raymond Zhou
  4. Khachik Khachikyan
  5. Gang Wu
  6. Stuart M Haslam
  7. Patil Kavarian
  8. Anne Dell
  9. Michael Demetriou  Is a corresponding author
  1. University of California, Irvine, United States
  2. Imperial College London, United Kingdom
https://doi.org/10.7554/eLife.14814
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  1. Haik Mkhikian
  2. Christie-Lynn Mortales
  3. Raymond Zhou
  4. Khachik Khachikyan
  5. Gang Wu
  6. Stuart M Haslam
  7. Patil Kavarian
  8. Anne Dell
  9. Michael Demetriou
(2016)
Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
eLife 5:e14814.
https://doi.org/10.7554/eLife.14814
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Abstract

Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme β1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly-LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly-LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self-correcting feature of the Golgi that sustains cellular homeostasis.

Article and author information

Author details

  1. Haik Mkhikian

    Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Christie-Lynn Mortales

    Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Raymond Zhou

    Department of Neurology and Institute for Immunology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Khachik Khachikyan

    Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Gang Wu

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Stuart M Haslam

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Patil Kavarian

    Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Anne Dell

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  9. Michael Demetriou

    Department of Neurology and Institute for Immunology, University of California, Irvine, Irvine, United States
    For correspondence
    mdemetri@uci.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Benjamin S Glick, The University of Chicago, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2001-2305) of the University of California, Irvine.

Human subjects: Informed consent was obtained from human subjects to obtain peripheral blood for isolation of T cells and that resulting publications and/or presentations will not contain identifiable information. This was approved by the University of California Irvine Institutional Review board (HS#2001-2075).

Version history

  1. Received: January 29, 2016
  2. Accepted: June 7, 2016
  3. Accepted Manuscript published: June 8, 2016 (version 1)
  4. Version of Record published: July 11, 2016 (version 2)

Copyright

© 2016, Mkhikian et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Haik Mkhikian
  2. Christie-Lynn Mortales
  3. Raymond Zhou
  4. Khachik Khachikyan
  5. Gang Wu
  6. Stuart M Haslam
  7. Patil Kavarian
  8. Anne Dell
  9. Michael Demetriou
(2016)
Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
eLife 5:e14814.
https://doi.org/10.7554/eLife.14814

Share this article

https://doi.org/10.7554/eLife.14814

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