PXD002165

PXD002165 is an original dataset announced via ProteomeXchange.

Title	Cell differentiation in Trypanosoma brucei is a bistable developmental switch requiring new protein synthesis to achieve signal memory
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:24:01.944.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Urbaniak
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-05-12 00:12:40	ID requested
1	2018-05-08 08:27:30	announced
⏵ 2	2024-10-22 04:24:02	announced	2024-10-22: Updated project metadata.

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;

curator keyword: Biological

submitter keyword: Phosphoproteomics, SILAC, differentiation,Trypanosoma brucei

Michael Daniel Urbaniak
contact affiliation	Biomedical & Life Sciences, Lancaster University, UK.
contact email	m.urbaniak@lancaster.ac.uk
lab head
Michael Urbaniak
contact affiliation	Lancaster University
contact email	m.urbaniak@lancaster.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002165
     1. Label: PRIDE project
     2. Name: Cell differentiation in Trypanosoma brucei is a bistable developmental switch requiring new protein synthesis to achieve signal memory