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

Michael V. Tran; Daria Khuntsariya; Richard D. Fetter; James W. Ferguson; Jennifer T. Wang; Alexandra F. Long; Lauren E. Cote; Stephen R. Wellard; Nabor Vázquez-Martínez; Maria D. Sallee; Mariya Genova; Maria M. Magiera; Sani Eskinazi; Jessica D. Lee; Nina Peel; Carsten Janke; Tim Stearns; Kang Shen; Zdenek Lansky; Jérémy Magescas; Jessica L. Feldman

doi:10.1016/j.devcel.2023.12.001

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

Michael V. Tran, Daria Khuntsariya, Richard D. Fetter, James W. Ferguson, Jennifer T. Wang, Alexandra F. Long, Lauren E. Cote, Stephen R. Wellard, Nabor Vázquez-Martínez, Maria D. Sallee, Mariya Genova, Maria M. Magiera, Sani Eskinazi, Jessica D. Lee, Nina Peel, Carsten Janke, Tim Stearns, Kang Shen, Zdenek Lansky, Jérémy MagescasJessica L. Feldman

Biology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Pages (from-to)	199-210.e11
Journal	Developmental Cell
Volume	59
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2023.12.001
State	Published - Jan 22 2024

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Funding

We thank Erwin Peterman, Guangshou Ou, Liqun Luo, and Kassandra Ori-McKenney for providing C. elegans strains, mice, protein, antibodies, and advice. We also thank members of the Feldman lab for helpful discussions about the manuscript. NIH (CMB training grant T32GM007276 [to M.V.T. and N.V.M.]; K99GM135489 [to M.D.S.], K99GM131024 [to J.T.W.], F32GM142181 [to A.F.L.], R01GM136902 and R01GM133950 [to J.L.F.], R01NS082208 [to K.S.], R35GM130286 and R01NS082208 [to T.S.], R15GM114727 and R15GM135886 [to N.P.]); AHA Postdoctoral Fellowships (to S.R.W. and J.W.F.); Damon Runyon Cancer Research Foundation Postdoctoral Fellowship DRG-2428-21 (to L.E.C.); Howard Hughes Medical Institute (to K.S.); Institut Curie , French National Research Agency award ANR-20-CE13-0011 , and Fondation pour la Recherche Médicale grant DEQ20170336756 (to C.J.); Fondation Vaincre Alzheimer FR-16055p and France Alzheimer grant 2023 (to M.M.M.); Institut Curie 3-I PhD Program (IC-3i) and EMBO short-term fellowship 8843 (to M.G.); Czech Science Foundation grant 19-27477X and CAS RVO : 86652036 (to Z.L.); and 1S10OD01227601 from the National Center for Research Resources (NCRR) supported this project, the contents of which do not necessarily represent the official views of the NCRR or the NIH. Some nematode strains were provided by the Caenorhabditis Genetic Center, which is funded by the NIH Office of Research Infrastructure Programs ( P40 OD010440 ).

Funders	Funder number
CAS RVO	86652036, 1S10OD01227601
Fondation Vaincre Alzheimer FR-16055p and France Alzheimer	2023
National Institutes of Health (NIH)	T32GM007276, R15GM114727, R01GM136902, K99GM131024, F32GM142181, R01GM133950, K99GM135489, R15GM135886, R01NS082208, R35GM130286
National Institutes of Health (NIH)
Howard Hughes Medical Institute
National Center for Research Resources	P40 OD010440
National Center for Research Resources
American the American Heart Association
Damon Runyon Cancer Research Foundation	DRG-2428-21
Damon Runyon Cancer Research Foundation
European Molecular Biology Organization
Agence Nationale de la Recherche	ANR-20-CE13-0011
Agence Nationale de la Recherche
Grantová Agentura České Republiky	19-27477X
Grantová Agentura České Republiky
Fondation pour la Recherche Médicale	DEQ20170336756
Fondation pour la Recherche Médicale
Institut Curie

Keywords

C. elegans
MAP9
axoneme
cilia
dynein
kinesin
microtubule
microtubule doublet
microtubule-associated protein
polyglutamylation

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2023.12.001

Cite this

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., ... Feldman, J. L. (2024). MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement. Developmental Cell, 59(2), 199-210.e11. https://doi.org/10.1016/j.devcel.2023.12.001

@article{89102f1343574713aa5eed35cc6267a8,

title = "MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement",

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.",

keywords = "C. elegans, MAP9, axoneme, cilia, dynein, kinesin, microtubule, microtubule doublet, microtubule-associated protein, polyglutamylation",

author = "Tran, \{Michael V.\} and Daria Khuntsariya and Fetter, \{Richard D.\} and Ferguson, \{James W.\} and Wang, \{Jennifer T.\} and Long, \{Alexandra F.\} and Cote, \{Lauren E.\} and Wellard, \{Stephen R.\} and Nabor V{\'a}zquez-Mart{\'i}nez and Sallee, \{Maria D.\} and Mariya Genova and Magiera, \{Maria M.\} and Sani Eskinazi and Lee, \{Jessica D.\} and Nina Peel and Carsten Janke and Tim Stearns and Kang Shen and Zdenek Lansky and J{\'e}r{\'e}my Magescas and Feldman, \{Jessica L.\}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2024",

month = jan,

day = "22",

doi = "10.1016/j.devcel.2023.12.001",

language = "English",

volume = "59",

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Tran, MV, Khuntsariya, D, Fetter, RD, Ferguson, JW, Wang, JT, Long, AF, Cote, LE, Wellard, SR, Vázquez-Martínez, N, Sallee, MD, Genova, M, Magiera, MM, Eskinazi, S, Lee, JD, Peel, N, Janke, C, Stearns, T, Shen, K, Lansky, Z, Magescas, J & Feldman, JL 2024, 'MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement', Developmental Cell, vol. 59, no. 2, pp. 199-210.e11. https://doi.org/10.1016/j.devcel.2023.12.001

TY - JOUR

T1 - MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement

AU - Tran, Michael V.

AU - Khuntsariya, Daria

AU - Fetter, Richard D.

AU - Ferguson, James W.

AU - Wang, Jennifer T.

AU - Long, Alexandra F.

AU - Cote, Lauren E.

AU - Wellard, Stephen R.

AU - Vázquez-Martínez, Nabor

AU - Sallee, Maria D.

AU - Genova, Mariya

AU - Magiera, Maria M.

AU - Eskinazi, Sani

AU - Lee, Jessica D.

AU - Peel, Nina

AU - Janke, Carsten

AU - Stearns, Tim

AU - Shen, Kang

AU - Lansky, Zdenek

AU - Magescas, Jérémy

AU - Feldman, Jessica L.

PY - 2024/1/22

Y1 - 2024/1/22

N2 - 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.

AB - 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.

KW - C. elegans

KW - MAP9

KW - axoneme

KW - cilia

KW - dynein

KW - kinesin

KW - microtubule

KW - microtubule doublet

KW - microtubule-associated protein

KW - polyglutamylation

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U2 - 10.1016/j.devcel.2023.12.001

DO - 10.1016/j.devcel.2023.12.001

M3 - Article

C2 - 38159567

AN - SCOPUS:85182334372

SN - 1534-5807

VL - 59

SP - 199-210.e11

JO - Developmental Cell

JF - Developmental Cell

IS - 2

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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