TY - JOUR TI - Glycan processing in the Golgi as optimal information coding that constrains cisternal number and enzyme specificity AU - Yadav, Alkesh AU - Vagne, Quentin AU - Sens, Pierre AU - Iyengar, Garud AU - Rao, Madan A2 - Campelo, Felix A2 - Pfeffer, Suzanne R VL - 11 PY - 2022 DA - 2022/02/17 SP - e76757 C1 - eLife 2022;11:e76757 DO - 10.7554/eLife.76757 UR - https://doi.org/10.7554/eLife.76757 AB - 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 realizes the desired target glycan distribution for a particular cell type and niche. In this article, we construct a simplified chemical synthesis model to quantitatively analyse the trade-offs 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 a 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. KW - glycan code KW - glycosylation KW - Golgi cisterna KW - enzyme specificity KW - optimization KW - Kullback-Leibler JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -