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Séminaire MSC
"Matière et Systèmes Complexes"

                      

Lundi 9 mars 2009 à 11h30
Bâtiment Condorcet, 4ème étage, salle 454 A.

Maxime Dahan
(Laboratoire Kastler-Brossel, ENS-paris)



Growth cones as amplifying and filtering modules during gradient sensing

Sensitivity to weak directional signals is a striking feature of chemotactic systems. In eukaryotic cells, it is often attributed to spatial amplification in the detection of the gradient of guidance cues due to an asymmetric distribution of signaling molecules. By combining single-quantum dot imaging with a guidance assay, we probed the dynamics of GABA_A receptors (GABA_A Rs) in nerve growth cones. In the presence of a GABA gradient, we observed a lateral redistribution of the receptors towards the GABA source. This effect was both reversible and specific of GABA signals. Its functional implication was established by calcium imaging which showed that the redistribution was accompanied by an enhanced asymmetry of the calcium response. Furthermore, single quantum-dot tracking of GABA_A Rs revealed a “conveyor-belt” type of motion in which receptors randomly alternated between periods of free diffusion and of microtubule-dependent directed movement.

We therefore propose a model in which an asymmetric activation by the signaling gradient leads to oriented growth of the MTs which, in turn, contributes to an asymmetric distribution of the receptors and amplification in gradient sensing. This simple model for the formation of polarity at the cell membrane is supported by numerical simulations that describe with minimal hypothesis the results of our experiments. These simulations also provide predictions on the dependence of the
formation of polarity as a function of gradient parameters.
We will finally show our current effort to place neurons in microfluidic devices, to generate controlled gradients and to characterize the growth cone as a sensing, amplifying and filtering module.