TY - JOUR
T1 - In situ cryo-electron tomography reveals the asymmetric architecture of mammalian sperm axonemes
AU - Chen, Zhen
AU - Greenan, Garrett A.
AU - Shiozaki, Momoko
AU - Liu, Yanxin
AU - Skinner, Will M.
AU - Zhao, Xiaowei
AU - Zhao, Shumei
AU - Yan, Rui
AU - Yu, Zhiheng
AU - Lishko, Polina V.
AU - Agard, David A.
AU - Vale, Ronald D.
N1 - Funding Information:
We are grateful to members of the Vale and Agard laboratories for discussions and critical reading of the manuscript. We thank Shixin Yang from the cryo-EM facility at Janelia Research Campus for his assistance with data collection. We thank Caiying Guo for generously sharing the resources required for the mouse experiments. We thank Zanlin Yu, Eric Tse and David Bulkley in the University of California, San Fransisco (UCSF) EM core facility for their assistance with data collection. We thank Sam Li and Shawn Zheng at UCSF for suggestions on EM data processing. We thank Tom Goddard at UCSF for providing a script to mark coordinates of subtomograms. We used and appreciated computing resources at both the workstations at Janelia Research Campus and the HPC Facility at UCSF. Z.C. was supported by the Helen Hay Whitney Foundation Postdoctoral Fellowship. W.M.S. was supported by the National Science Foundation Graduate Research Fellowship Program under grant numbers DGE 1752814 and DGE 2146752. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. P.V.L. received funding from a Pew Biomedical Scholars Award and a GCRLE grant from the Global Consortium for Reproductive Longevity and Equality made possible by the Bia-Echo Foundation. D.A.A. received funding from NIH R35GM118099. R.D.V. received funding from NIH R35GM118106 and the Howard Hughes Medical Institute. The UCSF cryo-EM facility has been supported by NIH grants 1S10OD026881, 1S10OD020054 and 1S10OD021741.
Funding Information:
We are grateful to members of the Vale and Agard laboratories for discussions and critical reading of the manuscript. We thank Shixin Yang from the cryo-EM facility at Janelia Research Campus for his assistance with data collection. We thank Caiying Guo for generously sharing the resources required for the mouse experiments. We thank Zanlin Yu, Eric Tse and David Bulkley in the University of California, San Fransisco (UCSF) EM core facility for their assistance with data collection. We thank Sam Li and Shawn Zheng at UCSF for suggestions on EM data processing. We thank Tom Goddard at UCSF for providing a script to mark coordinates of subtomograms. We used and appreciated computing resources at both the workstations at Janelia Research Campus and the HPC Facility at UCSF. Z.C. was supported by the Helen Hay Whitney Foundation Postdoctoral Fellowship. W.M.S. was supported by the National Science Foundation Graduate Research Fellowship Program under grant numbers DGE 1752814 and DGE 2146752. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. P.V.L. received funding from a Pew Biomedical Scholars Award and a GCRLE grant from the Global Consortium for Reproductive Longevity and Equality made possible by the Bia-Echo Foundation. D.A.A. received funding from NIH R35GM118099. R.D.V. received funding from NIH R35GM118106 and the Howard Hughes Medical Institute. The UCSF cryo-EM facility has been supported by NIH grants 1S10OD026881, 1S10OD020054 and 1S10OD021741.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/3
Y1 - 2023/3
N2 - The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm, providing the highest-resolution structural information to date. Our subtomogram averages reveal mammalian sperm-specific protein complexes within the microtubules, the radial spokes and nexin–dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm-specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.
AB - The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm, providing the highest-resolution structural information to date. Our subtomogram averages reveal mammalian sperm-specific protein complexes within the microtubules, the radial spokes and nexin–dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm-specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.
UR - http://www.scopus.com/inward/record.url?scp=85145332591&partnerID=8YFLogxK
U2 - 10.1038/s41594-022-00861-0
DO - 10.1038/s41594-022-00861-0
M3 - Article
C2 - 36593309
AN - SCOPUS:85145332591
SN - 1545-9993
VL - 30
SP - 360
EP - 369
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 3
ER -