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

Michelle M. Shimogawa; Angeline S. Wijono; Hui Wang; Jiayan Zhang; Jihui Sha; Natasha Szombathy; Sabeeca Vadakkan; Paula Pelayo; Keya Jonnalagadda; James Wohlschlegel; Z. Hong Zhou; Kent L. Hill

doi:10.1038/s41467-023-40230-z

Nature Communications (Aug 2023)

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

Michelle M. Shimogawa,
Angeline S. Wijono,
Hui Wang,
Jiayan Zhang,
Jihui Sha,
Natasha Szombathy,
Sabeeca Vadakkan,
Paula Pelayo,
Keya Jonnalagadda,
James Wohlschlegel,
Z. Hong Zhou,
Kent L. Hill

Affiliations

Michelle M. Shimogawa: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Angeline S. Wijono: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Hui Wang: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Jiayan Zhang: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Jihui Sha: Department of Biological Chemistry, University of California Los Angeles
Natasha Szombathy: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Sabeeca Vadakkan: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Paula Pelayo: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Keya Jonnalagadda: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
James Wohlschlegel: Department of Biological Chemistry, University of California Los Angeles
Z. Hong Zhou: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles
Kent L. Hill: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles

DOI: https://doi.org/10.1038/s41467-023-40230-z
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 12

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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