Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity
- Raman Research Institute, India
- Institut Curie, CNRS UMR168, France
- Columbia University, United States
- 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
Article and author information
Author details
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
- Felix Campelo, The Barcelona Institute of Science and Technology, Spain
Publication history
- Received: January 4, 2022
- Accepted: January 31, 2022
- 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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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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