scholarly journals Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Tina Freisinger ◽  
Ben Klünder ◽  
Jared Johnson ◽  
Nikola Müller ◽  
Garwin Pichler ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Positive Feedback ◽  
Feedback Loops

scholarly journals Mechanistic mathematical model of polarity in yeast

2012 ◽  
Vol 23 (10) ◽  
pp. 1998-2013 ◽  
Author(s):  
Natasha S. Savage ◽  
Anita T. Layton ◽  
Daniel J. Lew
Keyword(s):  
Cell Polarity ◽  
Positive Feedback ◽  
Reaction Diffusion ◽  
Feedback Loops ◽  
The Other ◽  
Fluorescence Recovery ◽  
Modeling Framework ◽  
Combined Model ◽  
Feedback Mechanisms ◽  
Vesicle Traffic

The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment.

scholarly journals Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity

2017 ◽  
Vol 28 (3) ◽  
pp. 370-380 ◽  
Author(s):  
Andrew B. Goryachev ◽  
Marcin Leda
Keyword(s):  
Symmetry Breaking ◽  
G Protein ◽  
Cell Polarity ◽  
Positive Feedback ◽  
Molecular Mechanisms ◽  
Theoretical Models ◽  
Feedback Loops ◽  
Recent Developments ◽  
Cellular Polarization ◽  
Generic System

Mathematical modeling has been instrumental in identifying common principles of cell polarity across diverse systems. These principles include positive feedback loops that are required to destabilize a spatially uniform state of the cell. The conserved small G-protein Cdc42 is a master regulator of eukaryotic cellular polarization. Here we discuss recent developments in studies of Cdc42 polarization in budding and fission yeasts and demonstrate that models describing symmetry-breaking polarization can be classified into six minimal classes based on the structure of positive feedback loops that activate and localize Cdc42. Owing to their generic system-independent nature, these model classes are also likely to be relevant for the G-protein–based symmetry-breaking systems of higher eukaryotes. We review experimental evidence pro et contra different theoretically plausible models and conclude that several parallel and non–mutually exclusive mechanisms are likely involved in cellular polarization of yeasts. This potential redundancy needs to be taken into consideration when interpreting the results of recent cell-rewiring studies.

scholarly journals FGF2 Translationally Induced by Hypoxia Is Involved in Negative and Positive Feedback Loops with HIF-1α

PLoS ONE ◽  
2008 ◽  
Vol 3 (8) ◽  
pp. e3078 ◽  
Author(s):  
Caroline Conte ◽  
Elodie Riant ◽  
Céline Toutain ◽  
Françoise Pujol ◽  
Jean-François Arnal ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loops

scholarly journals Understanding MAPK Signaling Pathways in Apoptosis

2020 ◽  
Vol 21 (7) ◽  
pp. 2346 ◽  
Author(s):  
Jicheng Yue ◽  
José M. López
Keyword(s):  
Signaling Pathways ◽  
Positive Feedback ◽  
Cell Model ◽  
Mapk Signaling ◽  
Feedback Loops ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Mechanisms ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most of these processes, such as apoptosis, MAPKs have a dual role since they can act as activators or inhibitors, depending on the cell type and the stimulus. In this review, we present the main pro- and anti-apoptotic mechanisms regulated by MAPKs, as well as the crosstalk observed between some MAPKs. We also describe the basic signaling properties of MAPKs (ultrasensitivity, hysteresis, digital response), and the presence of different positive feedback loops in apoptosis. We provide a simple guide to predict MAPKs’ behavior, based on the intensity and duration of the stimulus. Finally, we consider the role of MAPKs in osmostress-induced apoptosis by using Xenopus oocytes as a cell model. As we will see, apoptosis is plagued with multiple positive feedback loops. We hope this review will help to understand how MAPK signaling pathways engage irreversible cellular decisions.

scholarly journals Ultrasensitive gene regulation by positive feedback loops in nucleosome modification

2008 ◽  
Vol 4 (1) ◽  
pp. 182 ◽  
Author(s):  
Kim Sneppen ◽  
Mille A Micheelsen ◽  
Ian B Dodd
Keyword(s):  
Gene Regulation ◽  
Positive Feedback ◽  
Feedback Loops

scholarly journals Digital signaling network drives the assembly of the AIM2-ASC inflammasome

2018 ◽  
Vol 115 (9) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Mariusz Matyszewski ◽  
Seamus R. Morrone ◽  
Jungsan Sohn
Keyword(s):  
Host Defense ◽  
Positive Feedback ◽  
Signal Amplification ◽  
Molecular Level ◽  
Design Principles ◽  
Digital Circuit ◽  
Quantitative Model ◽  
Feedback Loops ◽  
Signaling Network

The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.

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