학술논문

3D structure and in situ arrangements of CatSper channel in the sperm flagellum.
Document Type
Academic Journal
Author
Zhao Y; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Wang H; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, 06510, USA.; Wiesehoefer C; Department of Anatomy, University of Duisburg-Essen, Medical Faculty, 45147, Essen, Germany.; Shah NB; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.; Molecular Biophysics and Integrative Bioimaging division, Bioscience Area, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.; Reetz E; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Hwang JY; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, 06510, USA.; Huang X; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, 06510, USA.; Wang TE; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, 06510, USA.; Lishko PV; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.; The Center for Reproductive Longevity and Equality, Buck Institute for Research on Aging, Novato, CA, 94945, USA.; Davies KM; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.; Molecular Biophysics and Integrative Bioimaging division, Bioscience Area, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.; Wennemuth G; Department of Anatomy, University of Duisburg-Essen, Medical Faculty, 45147, Essen, Germany.; Nicastro D; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Daniela.Nicastro@UTSouthwestern.edu.; Chung JJ; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, 06510, USA. jean-ju.chung@yale.edu.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, 06510, USA. jean-ju.chung@yale.edu.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca 2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9 -/- sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.
(© 2022. The Author(s).)