Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity

  1. Alkesh Yadav
  2. Quentin Vagne
  3. Pierre Sens
  4. Garud Iyengar  Is a corresponding author
  5. Madan Rao  Is a corresponding author
  1. Raman Research Institute, India
  2. Institut Curie, CNRS UMR168, France
  3. Columbia University, United States
  4. National Centre for Biological Sciences, India

Abstract

Many proteins that undergo sequential enzymatic modification in the Golgi cisternae are displayed at the plasma membrane as cell identity markers. The modified proteins, called glycans, represent a molecular code. The fidelity of this glycan code is measured by how accurately the glycan synthesis machinery realises the desired target glycan distribution for a particular cell type and niche. In this paper, we construct a simplified chemical synthesis model to quantitatively analyse the tradeoffs between the number of cisternae, and the number and specificity of enzymes, required to synthesize a prescribed target glycan distribution of a certain complexity to within a given fidelity. We find that to synthesize complex distributions, such as those observed in real cells, one needs to have multiple cisternae and precise enzyme partitioning in the Golgi. Additionally, for fixed number of enzymes and cisternae, there is an optimal level of specificity (promiscuity) of enzymes that achieves the target distribution with high fidelity. The geometry of the fidelity landscape in the multidimensional space of the number and specificity of enzymes, inter-cisternal transfer rates, and number of cisternae, provides a measure for robustness and identifies stiff and sloppy directions. Our results show how the complexity of the target glycan distribution and number of glycosylation enzymes places functional constraints on the Golgi cisternal number and enzyme specificity.

Data availability

The current manuscript is a computational study, so no data have been generated for this manuscript. The following repository on github contains the code and the data (numerical data + Mass Spec data) that are used in the paper: https://github.com/alkeshyadav/Glycosylation

The following data sets were generated

Article and author information

Author details

  1. Alkesh Yadav

    Raman Research Institute, Bangalore, India
    Competing interests
    No competing interests declared.
  2. Quentin Vagne

    Laboratoire Physico Chimie Curie, Institut Curie, CNRS UMR168, Paris, France
    Competing interests
    No competing interests declared.
  3. Pierre Sens

    Laboratoire Physico Chimie Curie, Institut Curie, CNRS UMR168, Paris, France
    Competing interests
    Pierre Sens, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4523-3791
  4. Garud Iyengar

    Industrial Engineering and Operations Research, Columbia University, New York, United States
    For correspondence
    garud@ieor.columbia.edu
    Competing interests
    No competing interests declared.
  5. Madan Rao

    Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Bangalore, India
    For correspondence
    madan@ncbs.res.in
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6210-6386

Funding

Department of Atomic Energy, Government of India (RTI4006)

  • Madan Rao

Simons Foundation (287975)

  • Madan Rao

JC Bose Fellowship (DST-SERB)

  • Madan Rao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Felix Campelo, The Barcelona Institute of Science and Technology, Spain

Publication history

  1. Received: January 4, 2022
  2. Accepted: January 31, 2022
  3. Accepted Manuscript published: February 17, 2022 (version 1)

Copyright

© 2022, Yadav 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. Alkesh Yadav
  2. Quentin Vagne
  3. Pierre Sens
  4. Garud Iyengar
  5. Madan Rao
(2022)
Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity
eLife 11:e76757.
https://doi.org/10.7554/eLife.76757

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