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FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction.
Shimogawa, Michelle M; Wijono, Angeline S; Wang, Hui; Zhang, Jiayan; Sha, Jihui; Szombathy, Natasha; Vadakkan, Sabeeca; Pelayo, Paula; Jonnalagadda, Keya; Wohlschlegel, James; Zhou, Z Hong; Hill, Kent L.
Afiliación
  • Shimogawa MM; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Wijono AS; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Wang H; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Zhang J; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Sha J; California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Szombathy N; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Vadakkan S; California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Pelayo P; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Jonnalagadda K; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Wohlschlegel J; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Zhou ZH; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Hill KL; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Nat Commun ; 14(1): 5225, 2023 08 26.
Article en En | MEDLINE | ID: mdl-37633952
ABSTRACT
Motility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) within DMTs influence axoneme stability and motility and provide lineage-specific adaptations, but individual MIP functions and assembly mechanisms are mostly unknown. Here, we show in the sleeping sickness parasite Trypanosoma brucei, that FAP106, a conserved MIP at the DMT inner junction, is required for trypanosome motility and functions as a critical interaction hub, directing assembly of several conserved and lineage-specific MIPs. We use comparative cryogenic electron tomography (cryoET) and quantitative proteomics to identify MIP candidates. Using RNAi knockdown together with fitting of AlphaFold models into cryoET maps, we demonstrate that one of these candidates, MC8, is a trypanosome-specific MIP required for parasite motility. Our work advances understanding of MIP assembly mechanisms and identifies lineage-specific motility proteins that are attractive targets to consider for therapeutic intervention.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cilios / Flagelos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cilios / Flagelos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos