Rab11 and Its Effector Rab Coupling Protein Contribute to the Trafficking of beta 1 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 alpha 9 promotes axon regeneration. We have therefore studied the mechanism by which alpha 9 integrin and its partner beta 1 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 beta 1 integrins in other cells. Rab11 colocalizes with alpha 9 and other alpha integrins and with beta 1 integrin in growth cones and axons, and immunopurified Rab11 vesicles contain alpha 9 and beta 1. Endocytosed beta 1 integrins traffic via Rab11. However, Rab11 vesicles in axons are generally static, and alpha 9 integrins undergo bouts of movement during which they leave the Rab11 compartment. In growth cones, alpha 9 and beta 1 overlap with RCP, particularly at the growth cone periphery. We show that beta 1 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 alpha 9 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