Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity.
|Title||Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Yadav A, Vagne Q, Sens P, Iyengar G, Rao M|
|Date Published||2022 Feb 17|
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.
|Grant List||RTI4006 / / Department of Atomic Energy, Government of India / |
287975 / / Simons Foundation /
DST-SERB / / JC Bose Fellowship /