The multi‐scale architecture of mammalian sperm flagella and implications for ciliary motility

Miguel Ricardo Leung, Marc C. Roelofs, Ravi Teja Ravi, Paula Maitan, Min Zhang, Heiko Henning, Elizabeth G. Bromfield, Stuart C. Howes, Bart M. Gadella, Hermes Bloomfield-Gadêlha, Tzviya Zeev-Ben-Mordehai*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
43 Downloads (Pure)

Abstract

Motile cilia are molecular machines used by a myriad of eukaryotic cells to swim through fluid environments. However, available molecular structures represent only a handful of cell types, limiting our understanding of how cilia are modified to support motility in diverse media. Here, we use cryo‐focused ion beam milling‐enabled cryo‐electron tomography to image sperm flagella from three mammalian species. We resolve in‐cell structures of centrioles, axonemal doublets, central pair apparatus, and endpiece singlets, revealing novel protofilament‐bridging microtubule inner proteins throughout the flagellum. We present native structures of the flagellar base, which is crucial for shaping the flagellar beat. We show that outer dense fibers are directly coupled to microtubule doublets in the principal piece but not in the midpiece. Thus, mammalian sperm flagella are ornamented across scales, from protofilament‐bracing structures reinforcing microtubules at the nano‐scale to accessory structures that impose micron‐scale asymmetries on the entire assembly. Our structures provide vital foundations for linking molecular structure to ciliary motility and evolution.
Original languageEnglish
Article numbere107410
Number of pages17
JournalEMBO Journal
Volume40
Issue number7
DOIs
Publication statusPublished - 10 Mar 2021

Bibliographical note

Funding Information:
The authors thank Dr. M. Vanevic for enabling this project with superb computational support; Dr. D. Vasishtan for providing scripts and advice that greatly facilitated subtomogram averaging; Ingr. C. T. W. M. Schneijdenberg and J. D. Meeldijk for management and maintenance of the Utrecht University EM Square facility; Stal Schep (Tull en het Waal, The Netherlands) for providing horse semen; M. W. Haaker and M. Houweling for providing mouse reproductive tracts; Prof. F. F?rster and Prof. A. Akhmanova for critical reading of the manuscript; and Prof. E. Y. Jones for insightful discussions. This work benefitted from access to the Netherlands Center for Electron Nanoscopy (NeCEN) with support from operators Dr. R. S. Dillard and Dr. C. Diebolder and IT support from B. Alewijnse. This work was funded by NWO Start-Up Grant 740.018.007 to T. Z., and M.R.L. is supported by a Clarendon Fund-Nuffield Department of Medicine Prize Studentship.

Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license

Keywords

  • centrioles
  • cryo-electron tomography
  • cryo-FIB milling
  • motile cilia
  • sperm

Fingerprint

Dive into the research topics of 'The multi‐scale architecture of mammalian sperm flagella and implications for ciliary motility'. Together they form a unique fingerprint.

Cite this