Preconditioning injury-induced neurite outgrowth of adult rat sensory neurons on fibronectin is mediated by mobilisation of axonal α5 integrin

Abstract

A preconditioning sciatic nerve crush promotes the capacity of adult sensory neurons to regenerate following a subsequent injury to their axons. The increase in regeneration is detected in cultures of dissociated neurons, as an earlier and enhanced rate of neurite elongation. We compare neurotrophin-stimulated neurite outgrowth from sensory neurons on laminin and fibronectin. There is a poor response of sensory neurons to fibronectin in comparison to laminin, but this is enhanced by a preconditioning lesion to the sciatic nerve 7 days prior to culture. By using specific integrin-binding fibronectin fragments and function-blocking antibodies, we demonstrate that the enhanced preconditioned neurite outgrowth on fibronectin is largely mediated by α5β1 integrin. Preconditioning injury alter the subcellular localisation of α5 integrin in preconditioned neurites. We show that α5 integrin localises to adhesion complexes in the growth cone and neurites of preconditioned neurons, but not control neurons.