3D Structure and in Situ Arrangements of CatSper Channel in the Sperm Flagellum

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 17

PMID 35715406

Authors

Yanhe Zhao

Huafeng Wang

Caroline Wiesehoefer

Naman B Shah

Evan Reetz

Jae Yeon Hwang

Xiaofang Huang

Tse-En Wang

Polina V Lishko

Karen M Davies

Gunther Wennemuth

Daniela Nicastro

Jean-Ju Chung

Affiliations

Soon will be listed here.

Abstract

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca 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.

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