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In human and animals, Arl13b is primarily associated with the ciliary membrane, where it acts as a guanine-nucleotide-exchange factor (GEF) for Arl3 and is implicated in a variety of ciliary and cellular functions. We have identified and characterized Trypanosoma brucei (Tb)Arl13, the sole Arl13b homolog in this evolutionarily divergent, protozoan parasite. TbArl13 has conserved flagellar functions and exhibits catalytic activity towards two different TbArl3 homologs. However, TbArl13 is distinctly associated with the axoneme through a dimerization\/docking (D\/D) domain. Replacing the D\/D domain with a sequence encoding a flagellar membrane protein created a viable alternative to the wild-type TbArl13 in our RNA interference (RNAi)-based rescue assay. Therefore, flagellar enrichment is crucial for TbArl13, but mechanisms to achieve this could be flexible. Our findings thus extend the understanding of the roles of Arl13b and Arl13b\u2013Arl3 pathway in a divergent flagellate of medical importance.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.219071","type":"journal-article","created":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T14:35:28Z","timestamp":1533911728000},"source":"Crossref","is-referenced-by-count":12,"title":["The unusual flagellar-targeting mechanism and functions of the trypanosome ortholog of the ciliary GTPase Arl13b"],"prefix":"10.1242","volume":"131","author":[{"given":"Yiliu","family":"Zhang","sequence":"first","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yameng","family":"Huang","sequence":"additional","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Srivathsan","sequence":"additional","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teck Kwang","family":"Lim","sequence":"additional","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Lin","sequence":"additional","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5506-2661","authenticated-orcid":false,"given":"Cynthia Y.","family":"He","sequence":"additional","affiliation":[{"name":"National University of Singapore Department of Biological Sciences, Faculty of Science , , 14 Science Drive 4 , Singapore \u2008 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,9,5]]},"reference":[{"key":"2024061317572432500_JCS219071C1","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkp851","article-title":"TriTrypDB: a functional genomic resource for the Trypanosomatidae","volume":"38","author":"Aslett","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2024061317572432500_JCS219071C2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1146\/annurev.genom.7.080505.115610","article-title":"The ciliopathies: an emerging class of human genetic disorders","volume":"7","author":"Badano","year":"2006","journal-title":"Annu. 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