Show simple item record

dc.contributor.authorMilde, Stefanen
dc.contributor.authorColeman, Michaelen
dc.date.accessioned2019-06-14T14:04:29Z
dc.date.available2019-06-14T14:04:29Z
dc.date.issued2014-11-21en
dc.identifier.issn1083-351X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/293626
dc.description.abstractThe NAD-synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is a critical survival factor for axons and its constant supply from neuronal cell bodies into axons is required for axon survival in primary culture neurites and axon extension in vivo. Recently, we showed that palmitoylation is necessary to target NMNAT2 to post-Golgi vesicles, thereby influencing its protein turnover and axon protective capacity. Here we find that NMNAT2 is a substrate for cytosolic thioesterases APT1 and APT2 and that palmitoylation/depalmitoylation dynamics are on a time scale similar to its short half-life. Interestingly, however, depalmitoylation does not release NMNAT2 from membranes. The mechanism of palmitoylation-independent membrane attachment appears to be mediated by the same minimal domain required for palmitoylation itself. Furthermore, we identify several zDHHC palmitoyltransferases that influence NMNAT2 palmitoylation and subcellular localization, among which a role for zDHHC17 (HIP14) in neuronal NMNAT2 palmitoylation is best supported by our data. These findings shed light on the enzymatic regulation of NMNAT2 palmitoylation and highlight individual thioesterases and palmitoyltransferases as potential targets to modulate NMNAT2-dependent axon survival.
dc.description.sponsorshipThis work was supported by a Medical Research Council studentship (to S. M.) and a Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant (to M. P. C.).
dc.languageengen
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAPT1en
dc.subjectAPT2en
dc.subjectEnzymeen
dc.subjectIntracellular Traffickingen
dc.subjectNMNAT2en
dc.subjectNeurodegenerationen
dc.subjectPalmitoyltransferaseen
dc.subjectProtein Acylationen
dc.subjectProtein Palmitoylationen
dc.subjectzDHHC17en
dc.subjectAcyltransferasesen
dc.subjectAnimalsen
dc.subjectAxonsen
dc.subjectBlotting, Westernen
dc.subjectCell Membraneen
dc.subjectCells, Cultureden
dc.subjectHEK293 Cellsen
dc.subjectHumansen
dc.subjectLipoylationen
dc.subjectMice, Inbred C57BLen
dc.subjectMutationen
dc.subjectNeuronsen
dc.subjectNicotinamide-Nucleotide Adenylyltransferaseen
dc.subjectPalmitic Aciden
dc.subjectPropiolactoneen
dc.subjectRNA Interferenceen
dc.subjectReverse Transcriptase Polymerase Chain Reactionen
dc.subjectSubstrate Specificityen
dc.subjectThiolester Hydrolasesen
dc.titleIdentification of palmitoyltransferase and thioesterase enzymes that control the subcellular localization of axon survival factor nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2).en
dc.typeArticle
prism.endingPage32870
prism.issueIdentifier47en
prism.publicationDate2014en
prism.publicationNameJournal of Biological Chemistryen
prism.startingPage32858
prism.volume289en
dc.identifier.doi10.17863/CAM.15582
dcterms.dateAccepted2014-09-29en
rioxxterms.versionofrecord10.1074/jbc.M114.582338en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2014-11-21en
dc.contributor.orcidColeman, Michael [0000-0002-9354-532X]
dc.identifier.eissn1083-351X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/L003813/1)
cam.issuedOnline2014-09-30en
dc.identifier.urlhttp://www.jbc.org/content/289/47/32858en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International