Oligopeptide signaling through TbGPR89 drives Trypanosome Quorum sensing

Federico Rojas, Eleanor Silvester, Julie Young, Rachel Milne, Mabel Tettey, Douglas R. Houston, Malcolm D. Walkinshaw, Irene Pérez-Pi, Manfred Auer, Helen Denton, Terry K. Smith, Joanne Thompson, Keith R. Matthews

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)306-317.e16
Number of pages28
JournalCell
Volume176
Issue number1-2
Early online date29 Nov 2018
DOIs
Publication statusPublished - 10 Jan 2019

Keywords / Materials (for Non-textual outputs)

  • trypanosoma brucei
  • parasite
  • quorum sensing
  • stumpy induction factor
  • differentiation
  • GPR89
  • oligopeptide
  • sleeping sickness

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