Collaborative Roles for RAC1, ERM Proteins and PTEN During Adult Sensory Axon Regeneration

The role of local of growth cone (GC) manipulation in adult regenerative systems is largely unexplored despite substantial translational importance. Here we investigated collaboration among Rac1 GTPase, its partnering ERM proteins and PTEN in adult sensory neurons and adult nerve regeneration. We confirmed expression of both Rac1 and ERM in adults and noted substantial impacts on neurite outgrowth in naïve and pre-injured adult sensory neurons. PTEN inhibition added to this outgrowth. Rac1 activation acted directly on adult GCs facilitating both attractive turning and advancement. In vivo regeneration indices including electrophysiological recovery, return of sensation, walking, repopulation of myelinated axons and reinnervation of the target epidermis indicated benefits of local Rac1 activation. These indices suggested maximal GC activation whereas local PTEN inhibition offered only limited added improvement. Our findings provide support for the concept of manipulating adult GCs, by emphasizing local Rac1 activation in directing therapy for nerve repair.