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FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction

Michelle M Shimogawa1, Angeline S Wijono1, Hui Wang1,2,3

  • 1Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Nature Communications
|August 26, 2023
PubMed

Insights

Flagellar inner proteins are crucial for parasite motility. This study identifies FAP106 and MC8 as key microtubule inner proteins (MIPs) essential for the motility of the sleeping sickness parasite Trypanosoma brucei.

Area of Science:

  • Cell Biology
  • Parasitology
  • Structural Biology

Background:

  • Flagellar motility in pathogenic protozoa relies on complex axonemal structures, including nine doublet microtubules (DMTs).
  • Microtubule inner proteins (MIPs) within DMTs are vital for axoneme stability and motility, yet their specific functions and assembly pathways remain largely uncharacterized.
  • Understanding these MIPs is critical for deciphering parasite locomotion and identifying potential therapeutic targets.

Purpose of the Study:

  • To investigate the function and assembly of Microtubule Inner Proteins (MIPs) in the flagella of Trypanosoma brucei.
  • To identify novel MIPs involved in parasite motility and understand their roles in axoneme structure.
  • To explore potential therapeutic targets for treating diseases caused by flagellated protozoa.

Main Methods:

  • Comparative cryogenic electron tomography (cryo-ET) was employed to visualize high-resolution axonemal structures.
  • Quantitative proteomics was used to identify and characterize MIP candidates within the DMTs.
  • RNA interference (RNAi) knockdown was performed to assess the functional importance of identified MIPs.
  • AlphaFold models were fitted into cryo-ET maps to determine the structural organization of MIPs.

Main Results:

  • FAP106, a conserved MIP located at the DMT inner junction, was found to be essential for Trypanosoma brucei motility.
  • FAP106 acts as a critical hub, orchestrating the assembly of multiple conserved and lineage-specific MIPs.
  • MC8, a trypanosome-specific MIP identified through proteomic and structural analyses, is indispensable for parasite motility.

Conclusions:

  • The study elucidates the assembly mechanisms of MIPs within the flagellar axoneme.
  • FAP106 and MC8 are identified as key regulators of parasite motility, highlighting their importance in flagellar function.
  • These lineage-specific motility proteins represent promising targets for the development of novel therapeutic interventions against parasitic diseases.

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