title: A comparative analysis of trypanosomatid SNARE proteins.
abstract: The Kinetoplastida are flagellated protozoa evolutionary distant and divergent from yeast and humans. Kinetoplastida include trypanosomatids, and a number of important pathogens. Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. inflict significant morbidity and mortality on humans and livestock as the etiological agents of human African trypanosomiasis, Chagas' disease and leishmaniasis respectively. For all of these organisms, intracellular trafficking is vital for maintenance of the host-pathogen interface, modulation/evasion of host immune system responses and nutrient uptake. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are critical components of the intracellular trafficking machinery in eukaryotes, mediating membrane fusion and contributing to organelle specificity. We asked how the SNARE complement evolved across the trypanosomatids. An in silico search of the predicted proteomes of T. b. brucei and T. cruzi was used to identify candidate SNARE sequences. Phylogenetic analysis, including comparisons with yeast and human SNAREs, allowed assignment of trypanosomatid SNAREs to the Q or R subclass, as well as identification of several SNAREs orthologous with those of opisthokonts. Only limited variation in number and identity of SNAREs was found, with Leishmania major having 27 and T. brucei 26, suggesting a stable SNARE complement post-speciation. Expression analysis of T. brucei SNAREs revealed significant differential expression between mammalian and insect infective forms, especially within R and Qb-SNARE subclasses, suggesting possible roles in adaptation to different environments. For trypanosome SNAREs with clear orthologs in opisthokonts, the subcellular localization of TbVAMP7C is endosomal while both TbSyn5 and TbSyn16B are at the Golgi complex, which suggests conservation of localization and possibly also function. Despite highly distinct life styles, the complement of trypanosomatid SNAREs is quite stable between the three pathogenic lineages, suggesting establishment in the last common ancestor of trypanosomes and Leishmania. Developmental changes to SNARE mRNA levels between blood steam and procyclic life stages suggest that trypanosomes modulate SNARE functions via expression. Finally, the locations of some conserved SNAREs have been retained across the eukaryotic lineage.
authors.affiliation: South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa.
authors.forename: Edwin
authors.initials: E
authors.lastname: Murungi
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Lael D
authors.initials: LD
authors.lastname: Barlow
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Divya
authors.initials: D
authors.lastname: Venkatesh
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Vincent O
authors.initials: VO
authors.lastname: Adung'a
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Electronic address: dacks@ualberta.ca.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.affiliation: Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, Scotland DD1 5EH, UK. Electronic address: m.c.field@dundee.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
authors.affiliation: South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa. Electronic address: alan@sanbi.ac.za.
authors.forename: Alan
authors.initials: A
authors.lastname: Christoffels
mesh_terms: D005786:Gene Expression Regulation; D010802:Phylogeny; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000378:metabolism*
chemical_list: D050600:SNARE Proteins
keywords: Molecular evolution; SNARE; Trypanosoma; Vesicle trafficking