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.
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
- Madan Rao
- Madan Rao
- Madan Rao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Felix Campelo, The Barcelona Institute of Science and Technology, Spain
- Received: January 4, 2022
- Accepted: January 31, 2022
- Accepted Manuscript published: February 17, 2022 (version 1)
© 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.
Little is known about how muscle length affects residual force enhancement (rFE) in humans. We therefore investigated rFE at short, long, and very long muscle lengths within the human quadriceps and patellar tendon (PT) using conventional dynamometry with motion capture (rFETQ) and a new, non-invasive shear-wave tensiometry technique (rFEWS). Eleven healthy male participants performed submaximal (50% max.) EMG-matched fixed-end reference and stretch-hold contractions across these muscle lengths while muscle fascicle length changes of the vastus lateralis (VL) were captured using B-mode ultrasound. We found significant rFETQ at long (7±5%) and very long (12±8%), but not short (2±5%) muscle lengths, whereas rFEWS was only significant at the very long (38±27%), but not short (8±12%) or long (6±10%) muscle lengths. We also found significant relationships between VL fascicle length and rFETQ (r=0.63, p=.001) and rFEWS (r=0.52, p=.017), but relationships were not significant between VL fascicle stretch amplitude and rFETQ (r=0.33, p=.126) or rFEWS (r=0.29, p=.201). PT shear-wave speed-angle relationships did not agree with estimated PT force-angle relationships, which indicates that estimating PT loads from shear-wave tensiometry might be inaccurate. We conclude that increasing muscle length rather than stretch amplitude contributes more to rFE during submaximal voluntary contractions of the human quadriceps.
In addition to diffusive signals, cells in tissue also communicate via long, thin cellular protrusions, such as airinemes in zebrafish. Before establishing communication, cellular protrusions must find their target cell. Here, we demonstrate that the shapes of airinemes in zebrafish are consistent with a finite persistent random walk model. The probability of contacting the target cell is maximized for a balance between ballistic search (straight) and diffusive search (highly curved, random). We find that the curvature of airinemes in zebrafish, extracted from live-cell microscopy, is approximately the same value as the optimum in the simple persistent random walk model. We also explore the ability of the target cell to infer direction of the airineme’s source, finding that there is a theoretical trade-off between search optimality and directional information. This provides a framework to characterize the shape, and performance objectives, of non-canonical cellular protrusions in general.