Cited by 18Genetic and Kidney Cyst DiseasesMicrotubule and mitosis dynamicsCystic Fibrosis Research Advances

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement

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Tran, Michael V., Khuntsariya, Daria, Fetter, Richard D., Ferguson, James W., Wang, Jennifer T., Long, Alexandra F., Cote, Lauren E., Wellard, Stephen R. +13 more·2024·Developmental Cell

Published version of a preprint

Abstract

Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs.

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Crossref · 10.1016/j.devcel.2023.12.001

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Authors
Tran, M. V., Khuntsariya, D., Fetter, R. D., Ferguson, J. W., Wang, J. T., Long, A. F., Cote, L. E., Wellard, S. R., Vázquez-Martínez, N., Sallee, M. D., Genova, M., Magiera, M. M., Eskinazi, S., Lee, J. D., Peel, N., Janke, C., Stearns, T., Shen, K., Lansky, Z., Magescas, J., & Feldman, J. L.
Affiliations
  • Stanford University (US)
  • Czech Academy of Sciences (CZ)
  • Howard Hughes Medical Institute (US)
  • Centre National de la Recherche Scientifique (FR)
  • The College of New Jersey (US)
  • Stanford Medicine (US)
Corresponding author
  • Magescas, Jérémy
  • Feldman, Jessica L.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2024-01
Volume
59
Issue
2
Pages
199-210.e11
ISSN
1534-5807 (ISSN-L)
OpenAlex
W4390414505
Cited by
18
References
91
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 2
FWCI
2.99
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • PubMed Central (submittedVersion)
Funders
  • European Molecular Biology Organization
  • Fondation Vaincre Alzheimer
  • Agence Nationale de la Recherche (ANR-20-CE13-0011)
  • American Heart Association
  • Damon Runyon Cancer Research Foundation (DRG-2428-21)
  • National Institutes of Health (1S10OD01227601, F32GM142181, K99GM131024, K99GM135489, R01GM133950, R01GM136902, R01NS082208, R15GM114727, R15GM135886, R35GM130286, T32GM007276)
  • Howard Hughes Medical Institute
  • National Center for Research Resources (P40 OD010440)
  • Grantová Agentura České Republiky (19-27477X)
  • Fondation pour la Recherche Médicale (DEQ20170336756)
  • Institut Curie
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Keywords
doublet microtubules, axoneme, cilia, tubulin polyglutamylation, microtubule-associated proteins, Caenorhabditis elegans, ciliary ultrastructure

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