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dc.contributor.authorMilde, Stefan
dc.contributor.authorFox, A. Nicole
dc.contributor.authorFreeman, Marc R.
dc.contributor.authorColeman, Michael P.
dc.date2022-08-11T08:09:29.000
dc.date.accessioned2022-08-23T16:32:33Z
dc.date.available2022-08-23T16:32:33Z
dc.date.issued2013-09-03
dc.date.submitted2016-10-26
dc.identifier.citationSci Rep. 2013;3:2567. doi: 10.1038/srep02567. <a href="http://dx.doi.org/10.1038/srep02567">Link to article on publisher's site</a>
dc.identifier.issn2045-2322 (Linking)
dc.identifier.doi10.1038/srep02567
dc.identifier.pmid23995269
dc.identifier.urihttp://hdl.handle.net/20.500.14038/37908
dc.description.abstractThe NAD-synthesising enzyme Nmnat2 is a critical survival factor for axons in vitro and in vivo. We recently reported that loss of axonal transport vesicle association through mutations in its isoform-specific targeting and interaction domain (ISTID) reduces Nmnat2 ubiquitination, prolongs its half-life and boosts its axon protective capacity in primary culture neurons. Here, we report evidence for a role of ISTID sequences in tuning Nmnat2 localisation, stability and protective capacity in vivo. Deletion of central ISTID sequences abolishes vesicle association and increases protein stability of fluorescently tagged, transgenic Nmnat2 in mouse peripheral axons in vivo. Overexpression of fluorescently tagged Nmnat2 significantly delays Wallerian degeneration in these mice. Furthermore, while mammalian Nmnat2 is unable to protect transected Drosophila olfactory receptor neuron axons in vivo, mutant Nmnat2s lacking ISTID regions substantially delay Wallerian degeneration. Together, our results establish Nmnat2 localisation and turnover as a valuable target for modulating axon degeneration in vivo.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23995269&dopt=Abstract">Link to Article in PubMed</a>
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectNeuroscience and Neurobiology
dc.titleDeletions within its subcellular targeting domain enhance the axon protective capacity of Nmnat2 in vivo
dc.typeJournal Article
dc.source.journaltitleScientific reports
dc.source.volume3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1177&amp;context=neurobiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/neurobiology_pp/178
dc.identifier.contextkey9309176
refterms.dateFOA2022-08-23T16:32:33Z
html.description.abstract<p>The NAD-synthesising enzyme Nmnat2 is a critical survival factor for axons in vitro and in vivo. We recently reported that loss of axonal transport vesicle association through mutations in its isoform-specific targeting and interaction domain (ISTID) reduces Nmnat2 ubiquitination, prolongs its half-life and boosts its axon protective capacity in primary culture neurons. Here, we report evidence for a role of ISTID sequences in tuning Nmnat2 localisation, stability and protective capacity in vivo. Deletion of central ISTID sequences abolishes vesicle association and increases protein stability of fluorescently tagged, transgenic Nmnat2 in mouse peripheral axons in vivo. Overexpression of fluorescently tagged Nmnat2 significantly delays Wallerian degeneration in these mice. Furthermore, while mammalian Nmnat2 is unable to protect transected Drosophila olfactory receptor neuron axons in vivo, mutant Nmnat2s lacking ISTID regions substantially delay Wallerian degeneration. Together, our results establish Nmnat2 localisation and turnover as a valuable target for modulating axon degeneration in vivo.</p>
dc.identifier.submissionpathneurobiology_pp/178
dc.contributor.departmentFreeman Lab
dc.contributor.departmentNeurobiology
dc.source.pages2567


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