ARF6 and Rab11 as intrinsic regulators of axon regeneration

Adult central nervous system (CNS) axons do not regenerate after injury due to both external inhibitory factors and a reduced internal capacity for growth. This is different from developing CNS neurons, which have a better regenerative ability that they lose as they mature. The small GTPases ARF6 and Rab11 play roles as intrinsic regulators of polarized transport and axon regeneration. As CNS axons mature, ARF6 activation prevents the axonal transport of integrins in Rab11 endosomes, constraining them to the somato-dendritic domain. Decreasing ARF6 activation allows axonal transport of integrins, which increases regenerative ability. These findings suggest new targets for promoting axon regeneration after CNS injury.

• 1
  ARF6 activation prevents the axonal transport of integrins in Rab11 endosomes in mature CNS axons, restricting them to the somato-dendritic domain.
• 2
  Decreasing ARF6 activation enables axonal transport of integrins, enhancing regenerative capacity, suggesting ARF6 activation state is an intrinsic determinant of regenerative capacity.
• 3
  Overexpression of Rab11 increased the regeneration potential and length of cortical neurons after laser axotomy, while also increasing the amount of integrins present in axons.