A mechanism for the polarity formation of chemoreceptors at the growth cone membrane for gradient amplification during directional sensing - École polytechnique Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2010

A mechanism for the polarity formation of chemoreceptors at the growth cone membrane for gradient amplification during directional sensing

Résumé

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. Cop. 2010 Bouzigues et al.
Fichier principal
Vignette du fichier
A_mechanism_PLOS.pdf (566.58 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-00804603 , version 1 (09-05-2014)

Identifiants

Citer

Cédric Bouzigues, D. Holcman, Maxime Dahan. A mechanism for the polarity formation of chemoreceptors at the growth cone membrane for gradient amplification during directional sensing. PLoS ONE, 2010, 5 (2), ⟨10.1371/journal.pone.0009243⟩. ⟨hal-00804603⟩
310 Consultations
147 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More