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The trypanosome flagellum is an essential organelle in multiple aspects of the parasites\u2019 development. The flagellar protein termed FLAgellar Member 8 (FLAM8) acts as a docking platform for a pool of cyclic AMP response protein 3 (CARP3) that is involved in signaling. FLAM8 exhibits a stage-specific distribution suggesting specific functions in the mammalian and vector stages of the parasite. Analyses of knockdown and knockout trypanosomes in their mammalian forms demonstrated that FLAM8 is not essential\n                    <jats:italic>in vitro<\/jats:italic>\n                    for survival, growth, motility and stumpy differentiation. Functional investigations in experimental infections showed that\n                    <jats:italic>FLAM8<\/jats:italic>\n                    -deprived trypanosomes can establish and maintain an infection in the blood circulation and differentiate into insect transmissible forms. However, quantitative bioluminescence imaging and gene expression analysis revealed that\n                    <jats:italic>FLAM8<\/jats:italic>\n                    -null parasites exhibit a significantly impaired dissemination in the extravascular compartment, that is restored by the addition of a single rescue copy of\n                    <jats:italic>FLAM8<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    trans-endothelial migration assays revealed significant defects in trypanosomes lacking\n                    <jats:italic>FLAM8<\/jats:italic>\n                    . FLAM8 is the first flagellar component shown to modulate\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    distribution in the host tissues, possibly through sensing functions, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches, especially in the skin.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011220","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T13:59:25Z","timestamp":1703167165000},"page":"e1011220","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["FLAgellum Member 8 modulates extravascular distribution of African 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