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PXD002165

PXD002165 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCell differentiation in Trypanosoma brucei is a bistable developmental switch requiring new protein synthesis to achieve signal memory
DescriptionThe life cycle of Trypanosoma brucei involves several cell differentiation transitions that allow transmission, survival and proliferation of these parasites. One of these transitions, the differentiation of growth-arrested stumpy forms in the mammalian blood into proliferating insect-stage procyclic forms, can be induced synchronously in vitro by addition of cis-aconitate (CA). Using single-cell analysis by flow-cytometry to follow differentiation, we show that this transition is an irreversible bistable switch where cells commit to differentiation after 1-3 hours of exposure to CA. This irreversibility implies the existence of positive feedback mechanisms that allow commitment to differentiation: i.e. the establishment of “memory” of exposure to the differentiation signal. Such mechanisms probably depend on post-translational modifications (e.g. phosphorylation) and/or synthesis of regulatory proteins. Using the reversible protein synthesis inhibitor cycloheximide, we find that protein synthesis is required for establishment of signal memory and normal commitment to differentiation. To characterize the ‘commitment proteome’, we performed SILAC phosphoproteomics to provide a detailed map of the protein expression and phosphorylation events during the early stages of differentiation in a synchronised parasite population. Using a rigorous candidate gene approach we have also demonstrated that the stumpy form enriched serine-throenine protein kinases TbNRKA/B stringently control the earliest events in differentiation identifying these kinases as major regulators of trypanosome development.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:24:01.944.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichael Urbaniak
SpeciesList scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationListphosphorylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-05-12 00:12:40ID requested
12018-05-08 08:27:30announced
22024-10-22 04:24:02announced2024-10-22: Updated project metadata.
Publication List
Domingo-Sananes MR, Sz, ö, ő, r B, Ferguson MA, Urbaniak MD, Matthews KR, Molecular control of irreversible bistability during trypanosome developmental commitment. J Cell Biol, 211(2):455-68(2015) [pubmed]
10.1083/jcb.201506114;
Keyword List
curator keyword: Biological
submitter keyword: Phosphoproteomics, SILAC, differentiation,Trypanosoma brucei
Contact List
Michael Daniel Urbaniak
contact affiliationBiomedical & Life Sciences, Lancaster University, UK.
contact emailm.urbaniak@lancaster.ac.uk
lab head
Michael Urbaniak
contact affiliationLancaster University
contact emailm.urbaniak@lancaster.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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