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A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules...

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Detalles Bibliográficos
Autores principales: Bouzigues, Cedric, Holcman, David, Dahan, Maxime
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825272/
https://www.ncbi.nlm.nih.gov/pubmed/20179770
http://dx.doi.org/10.1371/journal.pone.0009243
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author Bouzigues, Cedric
Holcman, David
Dahan, Maxime
author_facet Bouzigues, Cedric
Holcman, David
Dahan, Maxime
author_sort Bouzigues, Cedric
collection PubMed
description Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals.
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spelling pubmed-28252722010-02-24 A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing Bouzigues, Cedric Holcman, David Dahan, Maxime PLoS One Research Article Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals. Public Library of Science 2010-02-22 /pmc/articles/PMC2825272/ /pubmed/20179770 http://dx.doi.org/10.1371/journal.pone.0009243 Text en Bouzigues et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bouzigues, Cedric
Holcman, David
Dahan, Maxime
A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title_full A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title_fullStr A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title_full_unstemmed A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title_short A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing
title_sort mechanism for the polarity formation of chemoreceptors at the growth cone membrane for gradient amplification during directional sensing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825272/
https://www.ncbi.nlm.nih.gov/pubmed/20179770
http://dx.doi.org/10.1371/journal.pone.0009243
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