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PXD010632

PXD010632 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion
DescriptionWntless transports Wnt morphogens to the cell surface and is required for Wnt secretion and morphogenic gradients formation. Recycling of endocytosed Wntless requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi transport pathway. Here we demonstrate the essential role of SNX3-retromer assembly for Wntless transport and report that SNX3 associates with an evolutionary conserved endosome-associated membrane re-modelling complex composed of MON2, DOPEY2 and the putative aminophospholipid translocase, ATP9A. In vivo suppression of Ce-mon-2, Ce-pad-1 or Ce-tat-5 (respective MON2, DOPEY2 and ATP9A orthologues) phenocopy a loss of SNX3-retromer function, leading to enhanced lysosomal degradation of Wntless and a Wnt phenotype. Perturbed Wnt signalling is also observed upon overexpression of an ATPase-inhibited TAT-5(E246Q) mutant, suggesting a role for phospholipid flippase activity during SNX3-retromer-mediated Wntless sorting. Together, these findings provide in vitro and in vivo mechanistic details to describe SNX3-retromer-mediated transport during Wnt secretion and the formation of Wnt-morphogenic gradients.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:47:22.285.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKerrie McNally
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList6x(13)C labeled residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-07-31 07:33:09ID requested
12018-10-16 08:17:32announced
22018-12-04 03:56:56announcedUpdated project metadata.
32024-10-22 04:47:24announced2024-10-22: Updated project metadata.
Publication List
10.1038/s41467-018-06114-3;
McGough IJ, de Groot REA, Jellett AP, Betist MC, Varandas KC, Danson CM, Heesom KJ, Korswagen HC, Cullen PJ, SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion. Nat Commun, 9(1):3737(2018) [pubmed]
Keyword List
submitter keyword: retromer flippase snx3
Contact List
Peter J Cullen
contact affiliationUniversity of Bristol, School of Biochemistry
contact emailPete.cullen@bristol.ac.uk
lab head
Kerrie McNally
contact affiliationUniversity of Bristol
contact emailkm13610@bristol.ac.uk
dataset submitter
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Dataset FTP location
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