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FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction
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 ind...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460401/ https://www.ncbi.nlm.nih.gov/pubmed/37633952 http://dx.doi.org/10.1038/s41467-023-40230-z |
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author | 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. |
author_facet | 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. |
author_sort | Shimogawa, Michelle M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10460401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104604012023-08-28 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. Nat Commun Article 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. Nature Publishing Group UK 2023-08-26 /pmc/articles/PMC10460401/ /pubmed/37633952 http://dx.doi.org/10.1038/s41467-023-40230-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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. FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title | FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title_full | FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title_fullStr | FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title_full_unstemmed | FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title_short | FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
title_sort | fap106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460401/ https://www.ncbi.nlm.nih.gov/pubmed/37633952 http://dx.doi.org/10.1038/s41467-023-40230-z |
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