Structural specializations of the sperm tail

Miguel Ricardo Leung; Jianwei Zeng; Xiangli Wang; Marc C Roelofs; Wei Huang; Riccardo Zenezini Chiozzi; Johannes F Hevler; Albert J R Heck; Susan K Dutcher; Alan Brown; Rui Zhang; Tzviya Zeev-Ben-Mordehai

doi:10.1016/j.cell.2023.05.026

Structural specializations of the sperm tail

Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang, Marc C Roelofs, Wei Huang, Riccardo Zenezini Chiozzi, Johannes F Hevler, Albert J R Heck, Susan K Dutcher, Alan Brown, Rui Zhang, Tzviya Zeev-Ben-Mordehai

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

Abstract

Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which is increasing globally. Sperm are powered by a microtubule-based molecular machine-the axoneme-but it is unclear how axonemal microtubules are ornamented to support motility in diverse fertilization environments. Here, we present high-resolution structures of native axonemal doublet microtubules (DMTs) from sea urchin and bovine sperm, representing external and internal fertilizers. We identify >60 proteins decorating sperm DMTs; at least 15 are sperm associated and 16 are linked to infertility. By comparing DMTs across species and cell types, we define core microtubule inner proteins (MIPs) and analyze evolution of the tektin bundle. We identify conserved axonemal microtubule-associated proteins (MAPs) with unique tubulin-binding modes. Additionally, we identify a testis-specific serine/threonine kinase that links DMTs to outer dense fibers in mammalian sperm. Our study provides structural foundations for understanding sperm evolution, motility, and dysfunction at a molecular level.

Original language	English
Pages (from-to)	2880-2896.e17
Journal	Cell
Volume	186
Issue number	13
Early online date	13 Jun 2023
DOIs	https://doi.org/10.1016/j.cell.2023.05.026
Publication status	Published - 22 Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Funding

R.Z.C., J.F.H., and A.J.R.H. acknowledge support from the NWO X-omics Road Map program project 184.034.019. S.K.D. is supported by NIGMS grant R35-GM131909 . A.B. is supported by NIGMS grant R01GM141109 . This work was funded by NIGMS grant 1R01GM138854 (R.Z.) and NWO Start-Up Grant 740.018.007 (T.Z.). Electron microscopy of DMTs from Chlamydomonas flagella and sea urchin sperm was performed at either Washington University in St. Louis Center for Cellular Imaging (WUCCI) or Case Western Research University (CWRU). Imaging of DMTs from bovine sperm was performed at the Utrecht University (UU) Electron Microscopy Centre and at the Netherlands Centre for Electron Microscopy (NeCEN). We thank M. Rau (WUCCI), K. Li (CWRU), Ingr. C. Schneijdenberg, J. Meeldijk (UU), and Dr. W. Noteborn (NeCEN) for microscopy support. We acknowledge M. Naldrett and S. Alvarez at the Proteomics and Metabolomics Facility at the University of Nebraska-Lincoln for proteomics analysis of sea urchin sperm. We thank Dr. H. Henning and A. Rijneveld at the UU Veterinary Faculty for assistance with bovine sperm samples. We also thank Dr. M. Vanevic for computational support, Dr. S. Howes for valuable discussions on data collection and processing, Dr. H. Bloomfield-Gadelha for valuable discussions on microtubule biomechanics, and Prof. A. Akhmanova for critical reading of early versions of the manuscript. R.Z.C. J.F.H. and A.J.R.H. acknowledge support from the NWO X-omics Road Map program project 184.034.019. S.K.D. is supported by NIGMS grant R35-GM131909. A.B. is supported by NIGMS grant R01GM141109. This work was funded by NIGMS grant 1R01GM138854 (R.Z.) and NWO Start-Up Grant 740.018.007 (T.Z.). X.W. and J.Z. prepared sea urchin sperm for cryo-EM. M.R.L. and M.C.R. prepared bovine sperm samples for cryo-EM. M.R.L. J.Z. M.C.R. and W.H. collected cryo-EM data. M.R.L. M.C.R. and R.Z. processed cryo-EM data. J.Z. and M.R.L. identified proteins and built atomic models for sea urchin and bovine sperm. A.B. built atomic models for Chlamydomonas tektins. S.K.D. provided wild-type Chlamydomonas flagella. R.Z.C. and J.F.H. supervised by A.J.R.H. performed proteomics and cross-linking mass spectrometry experiments and corresponding data analysis for bovine sperm. M.R.L. A.B. R.Z. and T.Z. wrote the manuscript, and all authors contributed to revisions. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.

Funders	Funder number
National Institute of General Medical Sciences	R01GM141109, 1R01GM138854, R35-GM131909, 740.018.007
University of Nebraska-Lincoln
Case Western Reserve University
Universiteit Utrecht
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	184.034.019

Keywords

cryoelectron microscopy
microtubule associated proteins
microtubule inner proteins
motile cilia
sperm

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10.1016/j.cell.2023.05.026Licence: CC BY-NC-ND

1-s2.0-S0092867423005767-mainFinal published version, 21.3 MBLicence: CC BY-NC-ND

Cite this

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title = "Structural specializations of the sperm tail",

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AU - Heck, Albert J R

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AU - Brown, Alan

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AU - Zeev-Ben-Mordehai, Tzviya

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Structural specializations of the sperm tail

Abstract

Bibliographical note

Funding

Keywords

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