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Axonal localization of integrin receptors in the CNS is neuronal subtype and age dependent

Axonal localization of integrin receptors in the CNS is neuronal subtype and age dependent
Axonal localization of integrin receptors in the CNS is neuronal subtype and age dependent
The regenerative ability of CNS axons decreases with age however this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the alpha9 integrin subunit (tenascin-C receptor, ?9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally-expressed integrins (?9, ?6, or ?1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or co-transduction with its binding partner, ?1 integrin, did not induce integrin localization within axons. In contrast, virally-expressed ?9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype.

Significance Statement: Most CNS neurons have an intrinsically low ability to regenerate their axons. This study has asked whether the transport into axons of integrins, the receptors that mediate growth through extracellular matrix, might reveal reasons for the poor regenerative ability of CNS axons. Tagged integrins were expressed in sensory, retinal ganglion cell, cortical and red nucleus neurons. The integrins were transported down the axons of sensory and retinal ganglion cell axons, but not down the axons of adult cortical or red nucleus neurons. However, during the postnatal period of corticospinal axon growth, cortical neurons admitted integrins into their axons. The findings suggest that exclusion of integrins and other receptors from CNS axons may be a cause for their poor regenerative ability.
1-14
Andrews, Melissa
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Soleman, Sara
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Cheah, Menghon
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Tumbarello, David A.
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Mason, Matthew R.J.
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Moloney, Elizabeth
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Verhaagen, Joost
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Bensadoun, Jean-Charles
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Schneider, Bernard
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Aebischer, Patrick
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Fawcett, James W.
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Andrews, Melissa
ae987a2f-878e-4ae3-a7a3-a7170712096c
Soleman, Sara
98d4848c-2c1b-4f9a-a0ab-81c2f6ae7743
Cheah, Menghon
dcd039ed-e63d-4447-8494-08405fca83ec
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Mason, Matthew R.J.
10d47aa4-eb2a-495b-b365-d244ce11916f
Moloney, Elizabeth
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Verhaagen, Joost
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Bensadoun, Jean-Charles
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Schneider, Bernard
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Aebischer, Patrick
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Fawcett, James W.
4549730e-9f62-45b8-820b-8a9c98d1058b

Andrews, Melissa, Soleman, Sara, Cheah, Menghon, Tumbarello, David A., Mason, Matthew R.J., Moloney, Elizabeth, Verhaagen, Joost, Bensadoun, Jean-Charles, Schneider, Bernard, Aebischer, Patrick and Fawcett, James W. (2016) Axonal localization of integrin receptors in the CNS is neuronal subtype and age dependent. eNeuro, 3 (4), 1-14. (doi:10.1523/ENEURO.0029-16.2016).

Record type: Article

Abstract

The regenerative ability of CNS axons decreases with age however this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the alpha9 integrin subunit (tenascin-C receptor, ?9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally-expressed integrins (?9, ?6, or ?1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or co-transduction with its binding partner, ?1 integrin, did not induce integrin localization within axons. In contrast, virally-expressed ?9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype.

Significance Statement: Most CNS neurons have an intrinsically low ability to regenerate their axons. This study has asked whether the transport into axons of integrins, the receptors that mediate growth through extracellular matrix, might reveal reasons for the poor regenerative ability of CNS axons. Tagged integrins were expressed in sensory, retinal ganglion cell, cortical and red nucleus neurons. The integrins were transported down the axons of sensory and retinal ganglion cell axons, but not down the axons of adult cortical or red nucleus neurons. However, during the postnatal period of corticospinal axon growth, cortical neurons admitted integrins into their axons. The findings suggest that exclusion of integrins and other receptors from CNS axons may be a cause for their poor regenerative ability.

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Andrews MR et al_Axonal localization manuscript_27 June 2016_with figures.pdf - Accepted Manuscript
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ENEURO.0029-16.2016.full.pdf - Version of Record
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More information

Accepted/In Press date: 29 June 2016
e-pub ahead of print date: 7 July 2016
Published date: 7 July 2016
Organisations: Biomedicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 397627
URI: http://eprints.soton.ac.uk/id/eprint/397627
PURE UUID: 322e4c06-ee94-432c-aee5-dda90ade041d
ORCID for Melissa Andrews: ORCID iD orcid.org/0000-0001-5960-5619
ORCID for David A. Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561

Catalogue record

Date deposited: 12 Jul 2016 08:28
Last modified: 17 Dec 2019 01:35

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