a mechanism for the polarity formation of chemoreceptors at the growth cone membrane for gradient amplification during directional sensing的机制极性生长锥膜的化学感受器的形成梯度在定向传感放大.pdfVIP

A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing 1 2 2,3 Cedric Bouzigues *, David Holcman , Maxime Dahan ´ ´ 1 Laboratoire Optique et Biosciences, Inserm U696, CNRS 7645, Ecole Polytechnique, Palaiseau, France, 2 Departement de Biologie, Ecole Normale Superieure, Paris, ´ ´ France, 3 Laboratoire Kastler Brossel, CNRS UMR 8552, Ecole Normale Superieure, Universite Pierre et Marie Curie-Paris 6, Paris, France Abstract 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