Rab11 and its effector rab coupling protein contribute to the trafficking of β1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells

Integrins play an important part in axon growth, but integrin traffic in neurons is poorly understood. Expression of the tenascin-C-binding integrin α9 promotes axon regeneration. We have therefore studied the mechanism by which α9 integrin and its partner β1 are trafficked along axons and at the growth cone using adult DRG neurons and PC12 cells. We have focused on the small GTPase Rab11 and its effector Rab coupling protein (RCP), as they are involved in the long-range trafficking of β1 integrins in other cells. Rab11 colocalizes with α9 and other α integrins and with β1 integrin in growth cones and axons, and immunopurified Rab11 vesicles contain α9 and β1. Endocytosed β1 integrins traffic via Rab11. However, Rab11 vesicles in axons are generally static, and α9 integrins undergo bouts of movement during which they leave the Rab11 compartment. In growth cones, α9 and β1 overlap with RCP, particularly at the growth cone periphery. We show that β1 integrin trafficking during neurite outgrowth involves Rab11 and RCP, and that manipulation of these molecules alters surface integrin levels and axon growth, and can be used to enhance α9 integrin-dependent neurite outgrowth. Our data suggest that manipulation of trafficking via Rab11 and RCP could be a useful strategy for promoting integrin-dependent axonal regeneration.