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PXD021363

PXD021363 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleReceptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy
DescriptionAutophagosome formation requires multiple autophagy-related (ATG) factors. However, we find that a subset of autophagy substrates remains robustly targeted to the lysosome in the absence of several core ATGs, including the LC3 lipidation machinery. To address this unexpected result, we performed genome-wide CRISPR screens identifying genes required for NBR1 flux in ATG7KO cells. We find that ATG7-independent autophagy still requires canonical ATG factors including FIP200. However, in the absence of LC3 lipidation, additional factors are required including TAX1BP1 and TBK1. TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. In support of this model, we define a ubiquitin-independent mode of TAX1BP1 recruitment to NBR1 puncta, highlighting that TAX1BP1 recruitment and clustering, rather than ubiquitin binding per se, is critical for function. Collectively, our data provide a mechanistic basis for reports of selective autophagy in cells lacking the lipidation machinery, wherein receptor-mediated clustering of upstream autophagy factors drives continued autophagosome formation.
HostingRepositoryMassIVE
AnnounceDate2020-09-08
AnnouncementXMLSubmission_2020-09-08_10:32:53.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMark Adamo
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Oxidation
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-08 10:25:24ID requested
12020-09-08 10:32:53announced
Publication List
no publication
Keyword List
submitter keyword: Autophagosome, ATG, lysosome, LC3, NBR1, ATG7, FIP200, lipidation, TAX1BP1, TBK1, clustering, ubiquitin, autophagy
Contact List
Arminja Kettenbach
contact affiliationThe Geisel School of Medicine at Dartmouth
contact emailarminja.n.kettenbach@dartmouth.edu
lab head
Mark Adamo
contact affiliationDartmouth College
contact emailmark.e.adamo@dartmouth.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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