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

Richard Eva, Sarah Crisp, Jamie R. K Marland, Jim C Norman, Venkat Kanamarlapudi Orcid Logo, Charles ffrench-Constant, James W Fawcett

The Journal of Neuroscience, Volume: 32, Issue: 30, Pages: 10352 - 10364

Swansea University Author: Venkat Kanamarlapudi Orcid Logo

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DOI (Published version): 10.1523/JNEUROSCI.1409-12.2012

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 α9 integrin promotes axon regeneration, so we have investigated α9β1 trafficking and transport in axons and at...

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Published in: The Journal of Neuroscience
ISSN: 0270-6474
Published: 2012
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URI: https://cronfa.swan.ac.uk/Record/cronfa12274
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spelling 2019-07-16T13:57:19.1333519 v2 12274 2012-07-26 ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2012-07-26 BMS 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 α9 integrin promotes axon regeneration, so we have investigated α9β1 trafficking and transport in axons and at the growth cone. We have previously found that α9 and β1 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 α9 and β1 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 β1 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. Journal Article The Journal of Neuroscience 32 30 10352 10364 0270-6474 25 7 2012 2012-07-25 10.1523/JNEUROSCI.1409-12.2012 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-07-16T13:57:19.1333519 2012-07-26T12:47:23.5376238 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Richard Eva 1 Sarah Crisp 2 Jamie R. K Marland 3 Jim C Norman 4 Venkat Kanamarlapudi 0000-0002-8739-1483 5 Charles ffrench-Constant 6 James W Fawcett 7 0012274-16072019135708.pdf ARF6integrinTransportDRGNeuronsJNeuroSci12.pdf 2019-07-16T13:57:08.1030000 Output 2715423 application/pdf Not Applicable (or Unknown) true 2019-06-16T00:00:00.0000000 false eng
title ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
spellingShingle ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
Venkat Kanamarlapudi
title_short ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
title_full ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
title_fullStr ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
title_full_unstemmed ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
title_sort ARF6 Directs Axon Transport and Traffic of Integrins and Regulates Axon Growth in Adult DRG Neurons
author_id_str_mv 63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Venkat Kanamarlapudi
author2 Richard Eva
Sarah Crisp
Jamie R. K Marland
Jim C Norman
Venkat Kanamarlapudi
Charles ffrench-Constant
James W Fawcett
format Journal article
container_title The Journal of Neuroscience
container_volume 32
container_issue 30
container_start_page 10352
publishDate 2012
institution Swansea University
issn 0270-6474
doi_str_mv 10.1523/JNEUROSCI.1409-12.2012
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description 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 α9 integrin promotes axon regeneration, so we have investigated α9β1 trafficking and transport in axons and at the growth cone. We have previously found that α9 and β1 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 α9 and β1 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 β1 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.
published_date 2012-07-25T03:14:10Z
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