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Oligopeptide signaling through TbGPR89 drives trypanosome quorum sensing
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dc.contributor.author | Rojas, Federico | |
dc.contributor.author | Silvester, Eleanor | |
dc.contributor.author | Young, Julie | |
dc.contributor.author | Milne, Rachel | |
dc.contributor.author | Tettey, Mabel | |
dc.contributor.author | Houston, Douglas R. | |
dc.contributor.author | Walkinshaw, Malcolm D. | |
dc.contributor.author | Pérez-Pi, Irene | |
dc.contributor.author | Auer, Manfred | |
dc.contributor.author | Denton, Helen | |
dc.contributor.author | Smith, Terry K. | |
dc.contributor.author | Thompson, Joanne | |
dc.contributor.author | Matthews, Keith R. | |
dc.date.accessioned | 2018-12-19T09:30:04Z | |
dc.date.available | 2018-12-19T09:30:04Z | |
dc.date.issued | 2019-01-10 | |
dc.identifier | 256822743 | |
dc.identifier | c9069efb-361e-4a93-aeab-903e665e5bc0 | |
dc.identifier | 85058244935 | |
dc.identifier | 000455410800026 | |
dc.identifier.citation | Rojas , F , Silvester , E , Young , J , Milne , R , Tettey , M , Houston , D R , Walkinshaw , M D , Pérez-Pi , I , Auer , M , Denton , H , Smith , T K , Thompson , J & Matthews , K R 2019 , ' Oligopeptide signaling through Tb GPR89 drives trypanosome quorum sensing ' , Cell , vol. 176 , no. 1-2 , e16 , pp. 306-317 . https://doi.org/10.1016/j.cell.2018.10.041 | en |
dc.identifier.issn | 0092-8674 | |
dc.identifier.other | RIS: urn:A3A0506A31F06AEF2BB673B831C671B2 | |
dc.identifier.uri | https://hdl.handle.net/10023/16714 | |
dc.description | K.R.M. is funded by a Wellcome Trust Investigator Award (103740/Z14/Z) and a Royal Society Wolfson Research merit award (WM140045). The Medical Research Council (MR/M020118/1) supported T.K.S., and the Wellcome Trust supported J.T. (202094/Z/16/Z). M.A. received financial support from the Scottish Universities Life Sciences Alliance (SULSA; https://www.sulsa.ac.uk) and a Medical Research Council strategic grant (J54359). | en |
dc.description.abstract | Trypanosome parasites control their virulence and spread by using quorum sensing (QS) to generate transmissible “stumpy forms” in their host bloodstream. However, the QS signal “stumpy induction factor” (SIF) and its reception mechanism are unknown. Although trypanosomes lack G protein-coupled receptor signaling, we have identified a surface GPR89-family protein that regulates stumpy formation. TbGPR89 is expressed on bloodstream “slender form” trypanosomes, which receive the SIF signal, and when ectopically expressed, TbGPR89 drives stumpy formation in a SIF-pathway-dependent process. Structural modeling of TbGPR89 predicts unexpected similarity to oligopeptide transporters (POT), and when expressed in bacteria, TbGPR89 transports oligopeptides. Conversely, expression of an E. coli POT in trypanosomes drives parasite differentiation, and oligopeptides promote stumpy formation in vitro. Furthermore, the expression of secreted trypanosome oligopeptidases generates a paracrine signal that accelerates stumpy formation in vivo. Peptidase-generated oligopeptide QS signals being received through TbGPR89 provides a mechanism for both trypanosome SIF production and reception. | |
dc.format.extent | 12 | |
dc.format.extent | 5687118 | |
dc.language.iso | eng | |
dc.relation.ispartof | Cell | en |
dc.subject | Parasite | en |
dc.subject | Quorum sensing | en |
dc.subject | Stumpy induction factor | en |
dc.subject | Differentiation | en |
dc.subject | GPR89 | en |
dc.subject | Oligopeptide | en |
dc.subject | Sleeping sickness | en |
dc.subject | Trypanosome brucei | en |
dc.subject | QR180 Immunology | en |
dc.subject | DAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QR180 | en |
dc.title | Oligopeptide signaling through TbGPR89 drives trypanosome quorum sensing | en |
dc.type | Journal article | en |
dc.contributor.sponsor | Medical Research Council | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1016/j.cell.2018.10.041 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | MR/M020118/1 | en |
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