title: Assembling the components of the quorum sensing pathway in African trypanosomes.
abstract: African trypanosomes, parasites that cause human sleeping sickness, undergo a density-dependent differentiation in the bloodstream of their mammalian hosts. This process is driven by a released parasite-derived factor that causes parasites to accumulate in G1 and become quiescent. This is accompanied by morphological transformation to 'stumpy' forms that are adapted to survival and further development when taken up in the blood meal of tsetse flies, the vector for trypanosomiasis. Although the soluble signal driving differentiation to stumpy forms is unidentified, a recent genome-wide RNAi screen identified many of the intracellular signalling and effector molecules required for the response to this signal. These resemble components of nutritional starvation and quiescence pathways in other eukaryotes, suggesting that parasite development shares similarities with the adaptive quiescence of organisms such as yeasts and Dictyostelium in response to nutritional starvation and stress. Here, the trypanosome signalling pathway is discussed in the context of these conserved pathways and the possible contributions of opposing 'slender retainer' and 'stumpy inducer' arms described. As evolutionarily highly divergent eukaryotes, the organisation and conservation of this developmental pathway can provide insight into the developmental cycle of other protozoan parasites, as well as the adaptive and programmed developmental responses of all eukaryotic cells.
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh, EH9 3FL, UK.
authors: Binny M
authors: BM
authors: Mony
authors: Keith R
authors: KR
authors: Matthews
mesh_terms: D000818:Animals; D006801:Humans; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing; D015398:Signal Transduction; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000469:parasitology*
chemical_list: D015800:Protozoan Proteins
references: Mol Cell Biol. 2001 Jan;21(2):511-23
references: 11134339
references: Science. 2012 Dec 7;338(6112):1352-3
references: 23224556
references: Genes Dev. 2010 Jun 15;24(12):1306-16
references: 20551176
references: Eukaryot Cell. 2006 Jul;5(7):1126-35
references: 16835456
references: J Cell Sci. 2012 Oct 1;125(Pt 19):4423-33
references: 23132929
references: Mol Cell Biol. 2000 Feb;20(4):1321-8
references: 10648618
references: Genetics. 2012 Sep;192(1):73-105
references: 22964838
references: PLoS Pathog. 2013 May;9(5):e1003376
references: 23675305
references: J Cell Biol. 2006 Oct 23;175(2):293-303
references: 17043136
references: Eukaryot Cell. 2011 Jul;10(7):964-76
references: 21571922
references: Cell Host Microbe. 2011 Apr 21;9(4):310-8
references: 21501830
references: BMC Microbiol. 2014;14:51
references: 24575808
references: Mol Microbiol. 2001 Jul;41(1):33-46
references: 11454198
references: J Biol Chem. 2000 Jan 14;275(2):1449-56
references: 10625697
references: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19194-9
references: 17142316
references: Nature. 2009 May 14;459(7244):213-7
references: 19444208
references: Mol Biochem Parasitol. 1981 May;3(1):19-31
references: 6265773
references: Mol Cell Proteomics. 2011 Oct;10(10):M111.010538
references: 21685506
references: J Lab Physicians. 2011 Jan;3(1):4-11
references: 21701655
references: Cell Div. 2011 Oct 31;6:18
references: 22040655
references: Structure. 2009 Dec 9;17(12):1551-7
references: 20004158
references: PLoS One. 2009;4(10):e7532
references: 19855834
references: EMBO J. 2002 Jan 15;21(1-2):135-44
references: 11782433
references: Dev Growth Differ. 2011 May;53(4):482-94
references: 21521184
references: PLoS Pathog. 2014 Jan;10(1):e1003886
references: 24453978
references: Parasit Vectors. 2010 Sep 06;3:82
references: 20815940
references: Mol Biochem Parasitol. 2001 Apr 25;114(1):1-16
references: 11356509
references: Mol Biochem Parasitol. 1997 Dec 1;90(1):269-80
references: 9497048
references: Genes Dev. 1998 May 1;12(9):1356-70
references: 9573052
references: Cell. 1997 May 30;89(5):737-45
references: 9182761
references: Microbiol Mol Biol Rev. 1998 Dec;62(4):1264-300
references: 9841672
references: Elife. 2014;3:e02324
references: 24844706
references: Experientia. 1995 Dec 18;51(12):1124-34
references: 8536800
references: Genes Dev. 1998 Feb 15;12(4):586-97
references: 9472026
references: Mol Cell Biol. 1991 Aug;11(8):4045-52
references: 2072907
references: Development. 1998 Jun;125(12):2291-302
references: 9584128
references: J Bacteriol. 2000 Jun;182(12):3517-28
references: 10852885
references: Cell Microbiol. 2014 Apr;16(4):482-9
references: 24438230
references: J Protozool. 1989 Nov-Dec;36(6):572-7
references: 2600880
references: Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):E1676-84
references: 23572579
references: Eukaryot Cell. 2006 Apr;5(4):613-9
references: 16607008
references: PLoS Pathog. 2014 Jun;10(6):e1004178
references: 24945722
references: Mol Cell Proteomics. 2009 Jul;8(7):1527-38
references: 19346560
references: J Cell Sci. 1997 Nov;110 ( Pt 21):2661-71
references: 9427384
references: Mol Biochem Parasitol. 2002 Apr 9;120(2):269-83
references: 11897132
references: Annu Rev Genet. 2008;42:27-81
references: 18303986
references: Nat Chem Biol. 2011 Aug;7(8):512-8
references: 21769098
references: Mol Biochem Parasitol. 1986 Nov;21(2):189-97
references: 3537782
references: FEMS Microbiol Rev. 2012 Mar;36(2):306-39
references: 21658086
references: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8716-21
references: 15937117
references: PLoS One. 2012;7(10):e47621
references: 23118884
references: J R Soc Interface. 2009 Nov 6;6(40):959-78
references: 19674996
references: Parasitol Today. 1990 Jan;6(1):14-7
references: 15463248
references: Eukaryot Cell. 2010 Aug;9(8):1272-82
references: 20581292
references: Microbiol Mol Biol Rev. 2006 Dec;70(4):859-75
references: 17158701
references: Mol Biochem Parasitol. 2014 Jul;195(2):96-106
references: 24995711
references: Protist. 2008 Jan;159(1):137-51
references: 17931969
references: Nat Rev Microbiol. 2012 Jun;10(6):431-8
references: 22543519
references: Curr Opin Microbiol. 2011 Dec;14(6):676-81
references: 21962291
references: Mol Microbiol. 2004 Mar;51(6):1577-88
references: 15009886
references: Nature. 2014 Jan 30;505(7485):681-5
references: 24336212
references: Protist. 2001 Dec;152(4):367-78
references: 11822664
references: Nat Struct Mol Biol. 2004 Mar;11(3):226-33
references: 14981507
references: Exp Cell Res. 2006 Nov 1;312(18):3504-16
references: 16949574
references: EMBO J. 2007 May 2;26(9):2400-10
references: 17431399
references: Genome Res. 2011 Jun;21(6):915-24
references: 21363968
references: Trends Plant Sci. 2006 Mar;11(3):115-23
references: 16488176
references: Eukaryot Cell. 2014 Mar;13(3):412-26
references: 24442893
references: Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14399-404
references: 22908264
references: Mol Cell Biol. 2009 Nov;29(22):5975-88
references: 19797086
references: Nature. 1992 Mar 12;356(6365):171-2
references: 1312226
references: FASEB J. 2011 Feb;25(2):449-62
references: 21048044
references: J Proteome Res. 2013 May 3;12(5):2233-44
references: 23485197