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

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

Nat Commun. 2023 Aug 26;14(1):5225. doi: 10.1038/s41467-023-40230-z.

Authors

Michelle M Shimogawa¹, Angeline S Wijono¹, Hui Wang^{1

2

3}, Jiayan Zhang^{1

3

4}, Jihui Sha⁵, Natasha Szombathy¹, Sabeeca Vadakkan¹, Paula Pelayo¹, Keya Jonnalagadda¹, James Wohlschlegel⁵, Z Hong Zhou^{6

7

8}, Kent L Hill^{9

10

11}

Affiliations

¹ Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
² Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
³ California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁶ Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].
⁷ California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].
⁸ Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].
⁹ Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].
¹⁰ California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].
¹¹ Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA. [email protected].

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acclimatization
Axoneme
Cilia*
Flagella*
Microtubule Proteins
Microtubules

Substances

Microtubule Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding