Leishmania are flagellated eukaryotic parasites that cause leishmaniasis and are closely related to the other kinetoplastid parasites such as Trypanosoma brucei. In all these parasites there is a cell membrane invagination at the base of the flagellum called the flagellar pocket, which is tightly associated with and sculpted by cytoskeletal struc-tures including the flagellum attachment zone (FAZ). The FAZ is a complex intercon-nected structure linking the flagellum to the cell body and has critical roles in cell morphogenesis, function and pathogenicity. However, this structure varies dramati-cally in size and organisation between these different parasites, suggesting changes in protein localisation and function. Here, we screened the localisation and function of the Leishmania orthologues of T. brucei FAZ proteins identified in the genome-wide protein tagging project TrypTag. We identified 27 FAZ proteins and our deletion anal-ysis showed that deletion of two FAZ proteins in the flagellum, FAZ27 and FAZ34 resulted in a reduction in cell body size, and flagellum loss in some cells. Furthermore, after null mutant generation, we observed distinct and reproducible changes to cell shape, demonstrating the ability of the parasite to adapt to morphological perturba-tions resulting from gene deletion. This process of adaptation has important implica-tions for the study of Leishmania mutants.
Halliday, Clare de Liz, Laryssa Vanessa Vaughan, Sue Sunter, Jack D.
Department of Biological and Medical Sciences
Year of publication: 2023Date of RADAR deposit: 2023-11-20