Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing | Zendy

Federico Rojas | Zendy; Eleanor Silvester | Zendy; Julie Young | Zendy; Rachel Mary Milne | Zendy; Mabel Deladem Tettey | Zendy; Douglas R. Houston | Zendy; Malcolm D. Walkinshaw | Zendy; Irene PérezPi | Zendy; Manfred Auer | Zendy; Helen Denton | Zendy; Terry Smith | Zendy; Joanne Thompson | Zendy; Keith R. Matthews | Zendy

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Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing

Author(s) -

Federico Rojas,

Eleanor Silvester,

Julie Young,

Rachel Mary Milne,

Mabel Deladem Tettey,

Douglas R. Houston,

Malcolm D. Walkinshaw,

Irene PérezPi,

Manfred Auer,

Helen Denton,

Terry Smith,

Joanne Thompson,

Keith R. Matthews

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.10.041

Subject(s) - biology , quorum sensing , oligopeptide , signal transduction , microbiology and biotechnology , biofilm , genetics , bacteria , biochemistry , peptide

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.

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