Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG

Gradients of chemorepellent factors released from myelin may impair axon pathfinding and neuroregeneration after injury. We found that, analogously to the process of chemotaxis in invasive tumor cells, axonal growth cones of Xenopus spinal neurons modulate the functional distribution of integrin receptors during chemorepulsion induced by myelin-associated glycoprotein (MAG). A focal MAG gradient induced polarized endocytosis and concomitant asymmetric loss of beta(1)-integrin and vinculin-containing adhesions on the repellent side during repulsive turning. Loss of symmetrical beta(1)-integrin function was both necessary and sufficient for chemorepulsion, which required internalization by clathrin-mediated endocytosis. Induction of repulsive Ca(2+) signals was necessary and sufficient for the stimulated rapid endocytosis of beta(1)-integrin. Altogether, these findings identify beta(1)-integrin as an important functional cargo during Ca(2+)-dependent rapid endocytosis stimulated by a diffusible guidance cue. Such dynamic redistribution allows the growth cone to rapidly adjust adhesiveness across its axis, an essential feature for initiating chemotactic turning.