{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:36:47Z","timestamp":1791416207744,"version":"4.3.3"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>African trypanosomes, <jats:italic>Trypanosoma brucei<\/jats:italic> spp., are lethal pathogens that cause substantial human suffering and limit economic development in some of the world\u2019s most impoverished regions. The name <jats:italic>Trypanosoma<\/jats:italic> (\u201cauger cell\u201d) derives from the parasite\u2019s distinctive motility, which is driven by a single flagellum. However, despite decades of study, a requirement for trypanosome motility in mammalian host infection has not been established. LC1 is a conserved dynein subunit required for flagellar motility. Prior studies with a conditional RNAi-based LC1 mutant, RNAi-K\/R, revealed that parasites with defective motility could infect mice. However, RNAi-K\/R retained residual expression of wild-type LC1 and residual motility, thus precluding definitive interpretation. To overcome these limitations, here we generate constitutive mutants in which both LC1 alleles are replaced with mutant versions. These double knock-in mutants show reduced motility compared to RNAi-K\/R and are viable in culture, but are unable to maintain bloodstream infection in mice. The virulence defect is independent of infection route but dependent on an intact host immune system. By comparing different mutants, we also reveal a critical dependence on the LC1 N-terminus for motility and virulence. Our findings demonstrate that trypanosome motility is critical for establishment and maintenance of bloodstream infection, implicating dynein-dependent flagellar motility as a potential drug target.<\/jats:p>","DOI":"10.1038\/s41598-018-27228-0","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T09:48:23Z","timestamp":1528451303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Parasite motility is critical for virulence of African trypanosomes"],"prefix":"10.1038","volume":"8","author":[{"given":"Michelle M.","family":"Shimogawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunayan S.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville","family":"Kisalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-7085","authenticated-orcid":false,"given":"Yibo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanjie","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0717-683X","authenticated-orcid":false,"given":"Aydogan","family":"Ozcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent L.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,14]]},"reference":[{"key":"27228_CR1","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/nrmicro2009","volume":"6","author":"ML Ginger","year":"2008","unstructured":"Ginger, M. L., Portman, N. & McKean, P. G. Swimming with protists: perception, motility and flagellum assembly. Nat Rev Microbiol 6, 838\u2013850 (2008).","journal-title":"Nat Rev Microbiol"},{"key":"27228_CR2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.semcdb.2015.10.034","volume":"46","author":"T Kruger","year":"2015","unstructured":"Kruger, T. & Engstler, M. Flagellar motility in eukaryotic human parasites. Seminars in cell & developmental biology 46, 113\u2013127, https:\/\/doi.org\/10.1016\/j.semcdb.2015.10.034 (2015).","journal-title":"Seminars in cell & developmental biology"},{"key":"27228_CR3","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrmicro3274","volume":"12","author":"G Langousis","year":"2014","unstructured":"Langousis, G. & Hill, K. L. Motility and more: the flagellum of Trypanosoma brucei. Nat Rev Microbiol 12, 505\u2013518, https:\/\/doi.org\/10.1038\/nrmicro3274 (2014).","journal-title":"Nat Rev Microbiol"},{"key":"27228_CR4","doi-asserted-by":"publisher","unstructured":"Custodio, H. Protozoan Parasites. Pediatr. Rev. 37, 59\u201369; quiz 70\u201351, https:\/\/doi.org\/10.1542\/pir.2015-0006 (2016).","DOI":"10.1542\/pir.2015-0006"},{"key":"27228_CR5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4614-4726-9_1","volume":"764","author":"PJ Hotez","year":"2013","unstructured":"Hotez, P. J., Dumonteil, E., Heffernan, M. J. & Bottazzi, M. E. Innovation for the \u2018bottom 100 million\u2019: eliminating neglected tropical diseases in the Americas. Adv. Exp. Med. Biol. 764, 1\u201312 (2013).","journal-title":"Adv. Exp. Med. Biol."},{"key":"27228_CR6","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/S0140-6736(09)60233-6","volume":"373","author":"PJ Hotez","year":"2009","unstructured":"Hotez, P. J., Fenwick, A., Savioli, L. & Molyneux, D. H. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373, 1570\u20131575, https:\/\/doi.org\/10.1016\/S0140-6736(09)60233-6 (2009).","journal-title":"Lancet"},{"key":"27228_CR7","doi-asserted-by":"publisher","first-page":"e0005033","DOI":"10.1371\/journal.pntd.0005033","volume":"10","author":"J Manne-Goehler","year":"2016","unstructured":"Manne-Goehler, J., Umeh, C. A., Montgomery, S. P. & Wirtz, V. J. Estimating the Burden of Chagas Disease in the United States. PLoS Negl Trop Dis 10, e0005033, https:\/\/doi.org\/10.1371\/journal.pntd.0005033 (2016).","journal-title":"PLoS Negl Trop Dis"},{"key":"27228_CR8","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1073\/pnas.50.5.1002","volume":"50","author":"IR Gibbons","year":"1963","unstructured":"Gibbons, I. R. Studies on the Protein Components of Cilia from Tetrahymena Pyriformis. Proc. Natl. Acad. Sci. USA 50, 1002\u20131010 (1963).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"27228_CR9","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1002\/cm.970320203","volume":"32","author":"P Satir","year":"1995","unstructured":"Satir, P. Landmarks in cilia research from Leeuwenhoek to us. Cell Motil. Cytoskel. 32, 90\u201394 (1995).","journal-title":"Cell Motil. Cytoskel."},{"key":"27228_CR10","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1242\/jcs.004846","volume":"120","author":"DM Baron","year":"2007","unstructured":"Baron, D. M., Kabututu, Z. P. & Hill, K. L. Stuck in reverse: loss of LC1 in Trypanosoma brucei disrupts outer dynein arms and leads to reverse flagellar beat and backward movement. J. Cell Sci. 120, 1513\u20131520 (2007).","journal-title":"J. Cell Sci."},{"key":"27228_CR11","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1242\/jcs.03078","volume":"119","author":"C Branche","year":"2006","unstructured":"Branche, C. et al. Conserved and specific functions of axoneme components in trypanosome motility. J. Cell Sci. 119, 3443\u20133455 (2006).","journal-title":"J. Cell Sci."},{"key":"27228_CR12","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/cmi.12230","volume":"16","author":"B Rotureau","year":"2014","unstructured":"Rotureau, B., Ooi, C. P., Huet, D., Perrot, S. & Bastin, P. Forward motility is essential for trypanosome infection in the tsetse fly. Cell Microbiol 16, 425\u2013433, https:\/\/doi.org\/10.1111\/cmi.12230 (2014).","journal-title":"Cell Microbiol"},{"key":"27228_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nature04541","volume":"440","author":"R Broadhead","year":"2006","unstructured":"Broadhead, R. et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 440, 224\u2013227 (2006).","journal-title":"Nature"},{"key":"27228_CR14","doi-asserted-by":"publisher","unstructured":"Ralston, K. S. & Hill, K. L. Trypanin, a Component of the Flagellar Dynein Regulatory Complex, Is Essential in Bloodstream Form African Trypanosomes. PLoS Pathog 2, 873\u2013882, e101 https:\/\/doi.org\/10.1371\/journal.ppat.0020101 (2006).","DOI":"10.1371\/journal.ppat.0020101"},{"key":"27228_CR15","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.ijpara.2008.03.003","volume":"38","author":"KS Ralston","year":"2008","unstructured":"Ralston, K. S. & Hill, K. L. The flagellum of Trypanosoma brucei: new tricks from an old dog. Int. J. Parasitol. 38, 869\u2013884 (2008).","journal-title":"Int. J. Parasitol."},{"key":"27228_CR16","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1128\/EC.00298-10","volume":"10","author":"KS Ralston","year":"2011","unstructured":"Ralston, K. S., Kisalu, N. K. & Hill, K. L. Structure-function analysis of dynein light chain 1 identifies viable motility mutants in bloodstream-form Trypanosoma brucei. Euk Cell 10, 884\u2013894, https:\/\/doi.org\/10.1128\/EC.00298-10 (2011).","journal-title":"Euk Cell"},{"key":"27228_CR17","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1111\/cmi.12244","volume":"16","author":"NK Kisalu","year":"2014","unstructured":"Kisalu, N. K., Langousis, G., Bentolila, L. A., Ralston, K. S. & Hill, K. L. Mouse infection and pathogenesis by Trypanosoma brucei motility mutants. Cell Microbiol 16, 912\u2013924, https:\/\/doi.org\/10.1111\/cmi.12244 (2014).","journal-title":"Cell Microbiol"},{"key":"27228_CR18","doi-asserted-by":"publisher","first-page":"e25700","DOI":"10.1371\/journal.pone.0025700","volume":"7","author":"LC Hughes","year":"2012","unstructured":"Hughes, L. C., Ralston, K. S., Hill, K. L. & Zhou, Z. H. Three-dimensional structure of the Trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring. PLoS One 7, e25700, https:\/\/doi.org\/10.1371\/journal.pone.0025700 (2012).","journal-title":"PLoS One"},{"key":"27228_CR19","doi-asserted-by":"publisher","first-page":"4236","DOI":"10.1091\/mbc.e15-05-0289","volume":"26","author":"M Ichikawa","year":"2015","unstructured":"Ichikawa, M. et al. Axonemal dynein light chain-1 locates at the microtubule-binding domain of the gamma heavy chain. Mol. Biol. Cell 26, 4236\u20134247, https:\/\/doi.org\/10.1091\/mbc.E15-05-0289 (2015).","journal-title":"Mol. Biol. Cell"},{"key":"27228_CR20","doi-asserted-by":"publisher","first-page":"3108","DOI":"10.1074\/jbc.M111.286211","volume":"287","author":"SM King","year":"2012","unstructured":"King, S. M. & Patel-King, R. S. Functional architecture of the outer arm dynein conformational switch. J. Biol. Chem. 287, 3108\u20133122, https:\/\/doi.org\/10.1074\/jbc.M111.286211 (2012).","journal-title":"J. Biol. Chem."},{"key":"27228_CR21","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.cell.2007.08.046","volume":"131","author":"M Engstler","year":"2007","unstructured":"Engstler, M. et al. Hydrodynamic Flow-Mediated Protein Sorting on the Cell Surface of Trypanosomes. Cell 131, 505\u2013515 (2007).","journal-title":"Cell"},{"key":"27228_CR22","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/nrmicro2221","volume":"7","author":"MC Field","year":"2009","unstructured":"Field, M. C. & Carrington, M. The trypanosome flagellar pocket. Nat Rev Microbiol 7, 775\u2013786, https:\/\/doi.org\/10.1038\/nrmicro2221 (2009).","journal-title":"Nat Rev Microbiol"},{"key":"27228_CR23","doi-asserted-by":"publisher","first-page":"17425","DOI":"10.1073\/pnas.0909289106","volume":"106","author":"C Gadelha","year":"2009","unstructured":"Gadelha, C. et al. Membrane domains and flagellar pocket boundaries are influenced by the cytoskeleton in African trypanosomes. Proc. Natl. Acad. Sci. USA 106, 17425\u201317430, https:\/\/doi.org\/10.1073\/pnas.0909289106 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"27228_CR24","doi-asserted-by":"publisher","first-page":"e1005448","DOI":"10.1371\/journal.ppat.1005448","volume":"12","author":"JL Bargul","year":"2016","unstructured":"Bargul, J. L. et al. Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host. PLoS Pathog 12, e1005448, https:\/\/doi.org\/10.1371\/journal.ppat.1005448 (2016).","journal-title":"PLoS Pathog"},{"key":"27228_CR25","doi-asserted-by":"publisher","first-page":"e1003023","DOI":"10.1371\/journal.ppat.1003023","volume":"8","author":"N Heddergott","year":"2012","unstructured":"Heddergott, N. et al. Trypanosome motion represents an adaptation to the crowded environment of the vertebrate bloodstream. PLoS Pathog 8, e1003023, https:\/\/doi.org\/10.1371\/journal.ppat.1003023 (2012).","journal-title":"PLoS Pathog"},{"key":"27228_CR26","doi-asserted-by":"publisher","first-page":"19322","DOI":"10.1073\/pnas.0907001106","volume":"106","author":"JA Rodriguez","year":"2009","unstructured":"Rodriguez, J. A. et al. Propulsion of African trypanosomes is driven by bihelical waves with alternating chirality separated by kinks. Proc. Natl. Acad. Sci. USA 106, 19322\u201319327, https:\/\/doi.org\/10.1073\/pnas.0907001106 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"27228_CR27","first-page":"63","volume":"61","author":"ME Holwill","year":"1974","unstructured":"Holwill, M. E. Some physical aspects of the motility of ciliated and flagellated microorganisms. Sci. Prog. 61, 63\u201380 (1974).","journal-title":"Sci. Prog."},{"key":"27228_CR28","first-page":"1134","volume":"17","author":"M Gruby","year":"1843","unstructured":"Gruby, M. Recherches et observations sur une nouvelle esp\u00e8ce d\u2019h\u00e9matozoaire, Trypanosoma sanguinis. Comptes rendus hebdomadaire des s\u00e9ances de l\u2019Acad\u00e9mie des Sciences, Paris 17, 1134\u20131136 (1843).","journal-title":"Comptes rendus hebdomadaire des s\u00e9ances de l\u2019Acad\u00e9mie des Sciences, Paris"},{"key":"27228_CR29","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1128\/EC.2.2.200-208.2003","volume":"2","author":"KL Hill","year":"2003","unstructured":"Hill, K. L. Mechanism and biology of trypanosome cell motility. Euk Cell 2, 200\u2013208 (2003).","journal-title":"Euk Cell"},{"key":"27228_CR30","doi-asserted-by":"crossref","unstructured":"Jahn, T. L. & Bovee, E. C. In Infectious Blood Diseases of Man and Animals Vol. 1 (eds D. Weinman & M. Ristic) 393\u2013436 (Academic Press, 1968).","DOI":"10.1016\/B978-1-4832-2787-0.50020-0"},{"key":"27228_CR31","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nature10936","volume":"484","author":"AJ Firestone","year":"2012","unstructured":"Firestone, A. J. et al. Small-molecule inhibitors of the AAA\u2009+\u2009ATPase motor cytoplasmic dynein. Nature 484, 125\u2013129, https:\/\/doi.org\/10.1038\/nature10936 (2012).","journal-title":"Nature"},{"key":"27228_CR32","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/acschembio.5b00895","volume":"11","author":"SK See","year":"2016","unstructured":"See, S. K. et al. Cytoplasmic Dynein Antagonists with Improved Potency and Isoform Selectivity. ACS chemical biology 11, 53\u201360, https:\/\/doi.org\/10.1021\/acschembio.5b00895 (2016).","journal-title":"ACS chemical biology"},{"key":"27228_CR33","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.molbiopara.2017.04.003","volume":"214","author":"GS Reddy","year":"2017","unstructured":"Reddy, G. S., Mukhopadhyay, A. G. & Dey, C. S. Characterization of ciliobrevin A mediated dynein ATPase inhibition on flagellar motility of Leishmania donovani. Mol. Biochem. Parasitol. 214, 75\u201381, https:\/\/doi.org\/10.1016\/j.molbiopara.2017.04.003 (2017).","journal-title":"Mol. Biochem. Parasitol."},{"key":"27228_CR34","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev.micro.091208.073353","volume":"63","author":"KS Ralston","year":"2009","unstructured":"Ralston, K. S., Kabututu, Z. P., Melehani, J. H., Oberholzer, M. & Hill, K. L. The Trypanosoma brucei flagellum: moving parasites in new directions. Annu. Rev. Microbiol. 63, 335\u2013362, https:\/\/doi.org\/10.1146\/annurev.micro.091208.073353 (2009).","journal-title":"Annu. Rev. Microbiol."},{"key":"27228_CR35","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1111\/j.1600-0854.2007.00646.x","volume":"8","author":"B Wickstead","year":"2007","unstructured":"Wickstead, B. & Gull, K. Dyneins across eukaryotes: a comparative genomic analysis. Traffic 8, 1708\u20131721 (2007).","journal-title":"Traffic"},{"key":"27228_CR36","doi-asserted-by":"publisher","unstructured":"Capewell, P. et al. The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. eLife 5, https:\/\/doi.org\/10.7554\/eLife.17716 (2016).","DOI":"10.7554\/eLife.17716"},{"key":"27228_CR37","doi-asserted-by":"publisher","first-page":"e1005744","DOI":"10.1371\/journal.ppat.1005744","volume":"12","author":"G Caljon","year":"2016","unstructured":"Caljon, G. et al. The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies. PLoS Pathog 12, e1005744, https:\/\/doi.org\/10.1371\/journal.ppat.1005744 (2016).","journal-title":"PLoS Pathog"},{"key":"27228_CR38","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.chom.2016.05.002","volume":"19","author":"S Trindade","year":"2016","unstructured":"Trindade, S. et al. Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice. Cell Host Microbe 19, 837\u2013848, https:\/\/doi.org\/10.1016\/j.chom.2016.05.002 (2016).","journal-title":"Cell Host Microbe"},{"key":"27228_CR39","doi-asserted-by":"publisher","first-page":"8716","DOI":"10.1073\/pnas.0501886102","volume":"102","author":"K Sheader","year":"2005","unstructured":"Sheader, K. et al. Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes. Proc. Natl. Acad. Sci. USA 102, 8716\u20138721 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"27228_CR40","doi-asserted-by":"publisher","first-page":"e1006023","DOI":"10.1371\/journal.ppat.1006023","volume":"12","author":"JL Cheung","year":"2016","unstructured":"Cheung, J. L. et al. Blocking Synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei Leads to an Increase in Macrophage Phagocytosis Due to Reduced Clearance of Surface Coat Antibodies. PLoS Pathog 12, e1006023, https:\/\/doi.org\/10.1371\/journal.ppat.1006023 (2016).","journal-title":"PLoS Pathog"},{"key":"27228_CR41","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1365-3024.2005.00791.x","volume":"27","author":"JM Mansfield","year":"2005","unstructured":"Mansfield, J. M. & Paulnock, D. M. Regulation of innate and acquired immunity in African trypanosomiasis. Parasite Immunol. 27, 361\u2013371, https:\/\/doi.org\/10.1111\/j.1365-3024.2005.00791.x (2005).","journal-title":"Parasite Immunol."},{"key":"27228_CR42","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1083\/jcb.139.1.103","volume":"139","author":"H Webb","year":"1997","unstructured":"Webb, H. et al. The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice. J. Cell Biol. 139, 103\u2013114 (1997).","journal-title":"J. Cell Biol."},{"key":"27228_CR43","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1083\/jcb.200905083","volume":"186","author":"RS Patel-King","year":"2009","unstructured":"Patel-King, R. S. & King, S. M. An outer arm dynein light chain acts in a conformational switch for flagellar motility. J. Cell Biol. 186, 283\u2013295, https:\/\/doi.org\/10.1083\/jcb.200905083 (2009).","journal-title":"J. Cell Biol."},{"key":"27228_CR44","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1242\/jcs.03352","volume":"120","author":"DM Baron","year":"2007","unstructured":"Baron, D. M., Ralston, K. S., Kabututu, Z. P. & Hill, K. L. Functional genomics in Trypanosoma brucei identifies evolutionarily conserved components of motile flagella. J. Cell Sci. 120, 478\u2013491 (2007).","journal-title":"J. Cell Sci."},{"key":"27228_CR45","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.ajhg.2011.03.018","volume":"88","author":"M Mazor","year":"2011","unstructured":"Mazor, M. et al. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am. J. Hum. Genet. 88, 599\u2013607, https:\/\/doi.org\/10.1016\/j.ajhg.2011.03.018 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"27228_CR46","doi-asserted-by":"crossref","unstructured":"Imhof, S. & Hill, K. L. In Dyneins: Structure, Biology And Disease - Dynein Mechanics, Dysfunction, and Disease Vol. 2 (ed S. M. King) 418\u2013435 (Academic Press, Elsevier, 2018).","DOI":"10.1016\/B978-0-12-809470-9.00017-5"},{"key":"27228_CR47","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0091-679X(08)93002-8","volume":"93","author":"M Oberholzer","year":"2009","unstructured":"Oberholzer, M., Lopez, M. A., Ralston, K. S. & Hill, K. L. Approaches for functional analysis of flagellar proteins in African trypanosomes. Methods Cell Biol. 93, 21\u201357, https:\/\/doi.org\/10.1016\/S0091-679X(08)93002-8 (2009).","journal-title":"Methods Cell Biol."},{"key":"27228_CR48","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.molbiopara.2005.09.002","volume":"145","author":"M Oberholzer","year":"2006","unstructured":"Oberholzer, M., Morand, S., Kunz, S. & Seebeck, T. A vector series for rapid PCR-mediated C-terminal in situ tagging of Trypanosoma brucei genes. Mol. Biochem. Parasitol. 145, 117\u2013120 (2006).","journal-title":"Mol. Biochem. Parasitol."},{"key":"27228_CR49","doi-asserted-by":"publisher","first-page":"20273","DOI":"10.1074\/jbc.M114.579821","volume":"289","author":"W Bullard","year":"2014","unstructured":"Bullard, W., Lopes da Rosa-Spiegler, J., Liu, S., Wang, Y. & Sabatini, R. Identification of the glucosyltransferase that converts hydroxymethyluracil to base J in the trypanosomatid genome. J. Biol. Chem. 289, 20273\u201320282, https:\/\/doi.org\/10.1074\/jbc.M114.579821 (2014).","journal-title":"J. Biol. Chem."},{"key":"27228_CR50","doi-asserted-by":"publisher","first-page":"39369","DOI":"10.1074\/jbc.M006907200","volume":"275","author":"KL Hill","year":"2000","unstructured":"Hill, K. L., Hutchings, N. R., Grandgenett, P. M. & Donelson, J. E. T Lymphocyte triggering factor of African trypanosomes is associated with the flagellar fraction of the cytoskeleton and represents a new family of proteins that are present in several divergent eukaryotes. J. Biol. Chem. 275, 39369\u201339378 (2000).","journal-title":"J. Biol. Chem."},{"key":"27228_CR51","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1128\/EC.00019-14","volume":"13","author":"EA Saada","year":"2014","unstructured":"Saada, E. A. et al. Insect stage-specific receptor adenylate cyclases are localized to distinct subdomains of the Trypanosoma brucei Flagellar membrane. Euk Cell 13, 1064\u20131076, https:\/\/doi.org\/10.1128\/EC.00019-14 (2014).","journal-title":"Euk Cell"},{"key":"27228_CR52","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1128\/EC.4.3.516-525.2005","volume":"4","author":"C Gadelha","year":"2005","unstructured":"Gadelha, C., Wickstead, B., de Souza, W., Gull, K. & Cunha-e-Silva, N. Cryptic paraflagellar rod in endosymbiont-containing kinetoplastid protozoa. Euk Cell 4, 516\u2013525 (2005).","journal-title":"Euk Cell"},{"key":"27228_CR53","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/nmeth.1237","volume":"5","author":"K Jaqaman","year":"2008","unstructured":"Jaqaman, K. et al. Robust single-particle tracking in live-cell time-lapse sequences. Nature methods 5, 695\u2013702, https:\/\/doi.org\/10.1038\/nmeth.1237 (2008).","journal-title":"Nature methods"},{"key":"27228_CR54","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1083\/jcb.201307172","volume":"204","author":"N Tarantino","year":"2014","unstructured":"Tarantino, N. et al. TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures. J. Cell Biol. 204, 231\u2013245, https:\/\/doi.org\/10.1083\/jcb.201307172 (2014).","journal-title":"J. Cell Biol."},{"key":"27228_CR55","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1073\/pnas.1518079113","volume":"113","author":"G Langousis","year":"2016","unstructured":"Langousis, G. et al. Loss of the BBSome perturbs endocytic trafficking and disrupts virulence of Trypanosoma brucei. Proc. Natl. Acad. Sci. USA 113, 632\u2013637, https:\/\/doi.org\/10.1073\/pnas.1518079113 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27228-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27228-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27228-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:20:50Z","timestamp":1671603650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27228-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,14]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["27228"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-27228-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,14]]},"assertion":[{"value":"13 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9122"}}