ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons

Richard Eva, Sarah Crisp, Jamie Marland, Jim C. Norman, Venkateswarlu Kanamarlapudi, Charles Ffrench-Constant, James W. Fawcett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Integrins are involved in axon growth and regeneration. Manipulation of integrins is a route to promoting axon regeneration and understanding regeneration failure in the CNS. Expression of alpha 9 integrin promotes axon regeneration, so we have investigated alpha 9 beta 1 trafficking and transport in axons and at the growth cone. We have previously found that alpha 9 and beta 1 integrins traffic via Rab11-positive recycling endosomes in peripheral axons and growth cones. However, transport via Rab11 is slow, while rapid transport occurs in vesicles lacking Rab11. We have further studied alpha 9 and beta 1 integrin transport and traffic in adult rat dorsal root ganglion axons and PC12 cells. Integrins are in ARF6 vesicles during rapid axonal transport and during trafficking in the growth cone. We report that rapid axonal transport of these integrins and their trafficking at the cell surface is regulated by ARF6. ARF6 inactivation by expression of ACAP1 leads to increased recycling of beta 1 integrins to the neuronal surface and to increased anterograde axonal transport. ARF6 activation by expression of the neuronal guanine nucleotide exchange factors, ARNO or EFA6, increases retrograde integrin transport in axons and increases integrin internalization. ARF6 inactivation increases integrin-mediated outgrowth, while activation decreases it. The coordinated changes in integrin transport and recycling resulting from ARF6 activation or inactivation are the probable mechanism behind this regulation of axon growth. Our data suggest a novel mechanism of integrin traffic and transport in peripheral axons, regulated by the activation state of ARF6, and suggest that ARF6 might be targeted to enhance integrin-dependent axon regeneration after injury.

Original languageEnglish
Pages (from-to)10352-10364
Number of pages13
JournalJournal of Neuroscience
Volume32
Issue number30
DOIs
Publication statusPublished - 25 Jul 2012

Keywords

  • DEPENDENT MECHANISM
  • NEURITE OUTGROWTH
  • PLASMA-MEMBRANE
  • NUCLEOTIDE EXCHANGE FACTOR
  • SMALL G-PROTEINS
  • RIBOSYLATION FACTOR 6
  • CELL-ADHESION
  • SENSORY NEURONS
  • RECYCLING ENDOSOME
  • HIPPOCAMPAL-NEURONS

Fingerprint

Dive into the research topics of 'ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons'. Together they form a unique fingerprint.

Cite this