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Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene

Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism.
1097-6256
1199-1206
Mack, Till G.A.
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Reiner, Michael
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Beirowski, Bogdan
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Mi, Weiqian
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Emanelli, Monica
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Wagner, Diana
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Thomson, Derek
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Gillingwater, Tom
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Court, Felipe
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Conforti, Laura
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Fernando, F. Shama
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Tarlton, Andrea
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Anderssen, Christian
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Addicks, Klaus
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Magni, Giulio
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Ribchester, Richard R.
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Perry, V. Hugh
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Coleman, Michael P.
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Mack, Till G.A.
8dcde3a1-1e66-468c-b5fc-e32d5e249e94
Reiner, Michael
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Beirowski, Bogdan
c5956e7e-6177-46db-948a-a015cfe6f495
Mi, Weiqian
17920ef6-279b-4e6e-acc6-0070df31c5d1
Emanelli, Monica
ac554291-4635-48df-83a8-455387fb8238
Wagner, Diana
2af001d6-bc6c-4900-9976-389a8fbc4f54
Thomson, Derek
87c32f42-a519-49ca-a2e4-5aaa5686401a
Gillingwater, Tom
0b85275a-f94e-40e4-a10c-2d2e18068d45
Court, Felipe
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Conforti, Laura
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Fernando, F. Shama
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Tarlton, Andrea
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Anderssen, Christian
fee99641-9195-4dcc-8cdc-ab663a7373fe
Addicks, Klaus
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Magni, Giulio
ac56bf8b-0c3f-4920-9f8a-e38f4bfa310c
Ribchester, Richard R.
4bcfc164-f345-4795-a337-8c8bcc3c01de
Perry, V. Hugh
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Coleman, Michael P.
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Mack, Till G.A., Reiner, Michael, Beirowski, Bogdan, Mi, Weiqian, Emanelli, Monica, Wagner, Diana, Thomson, Derek, Gillingwater, Tom, Court, Felipe, Conforti, Laura, Fernando, F. Shama, Tarlton, Andrea, Anderssen, Christian, Addicks, Klaus, Magni, Giulio, Ribchester, Richard R., Perry, V. Hugh and Coleman, Michael P. (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nature Neuroscience, 4 (12), 1199-1206. (doi:10.1038/nn770).

Record type: Article

Abstract

Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism.

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Published date: 19 November 2001
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 24024
URI: http://eprints.soton.ac.uk/id/eprint/24024
ISSN: 1097-6256
PURE UUID: 09e15141-dd74-4d3a-879b-667da3c57bb0

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Date deposited: 17 Mar 2006
Last modified: 15 Mar 2024 06:51

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Contributors

Author: Till G.A. Mack
Author: Michael Reiner
Author: Bogdan Beirowski
Author: Weiqian Mi
Author: Monica Emanelli
Author: Diana Wagner
Author: Derek Thomson
Author: Tom Gillingwater
Author: Felipe Court
Author: Laura Conforti
Author: F. Shama Fernando
Author: Andrea Tarlton
Author: Christian Anderssen
Author: Klaus Addicks
Author: Giulio Magni
Author: Richard R. Ribchester
Author: V. Hugh Perry
Author: Michael P. Coleman

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