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

Abstract
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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

1. Yadav A
(2022) Glycan processing in the Golgi : optimal information coding and constraints on cisternal number and enzyme specificity
GitHub.

https://github.com/alkeshyadav/Glycosylation

Article and author information

Author details

Alkesh Yadav

Raman Research Institute, Bangalore, India

Competing interests
No competing interests declared.
Quentin Vagne

Laboratoire Physico Chimie Curie, Institut Curie, CNRS UMR168, Paris, France

Competing interests
No competing interests declared.
Pierre Sens

Laboratoire Physico Chimie Curie, Institut Curie, CNRS UMR168, Paris, France

Competing interests
Pierre Sens, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-4523-3791
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.
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.

"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.

Copyright

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.