C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane

[Display omitted] In mammalian sperm cells, regulation of spatiotemporal Ca2+ signaling relies on the quadrilinear Ca2+ signaling nanodomains in the flagellar membrane. The sperm-specific, multi-subunit CatSper Ca2+ channel, which is crucial for sperm hyperactivated motility and male fertility, orga...

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Bibliographic Details
Published inCell reports (Cambridge) Vol. 38; no. 3; p. 110226
Main Authors Hwang, Jae Yeon, Wang, Huafeng, Lu, Yonggang, Ikawa, Masahito, Chung, Jean-Ju
Format Journal Article
LanguageEnglish
Published Elsevier Inc 18.01.2022
Subjects
Ca2+ channel
Ca2+ signaling
CatSper
domain organization
flagellar membrane targeting
male fertility
sperm motility
CatSper
sperm motility
Ca2+ signaling
domain organization
Ca2+ channel
flagellar membrane targeting
male fertility
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Summary:[Display omitted] In mammalian sperm cells, regulation of spatiotemporal Ca2+ signaling relies on the quadrilinear Ca2+ signaling nanodomains in the flagellar membrane. The sperm-specific, multi-subunit CatSper Ca2+ channel, which is crucial for sperm hyperactivated motility and male fertility, organizes the nanodomains. Here, we report CatSperτ, the C2cd6-encoded membrane-associating C2 domain protein, can independently migrate to the flagella and serve as a major targeting component of the CatSper channel complex. CatSperτ loss of function in mice demonstrates that it is essential for sperm hyperactivated motility and male fertility. CatSperτ targets the CatSper channel into the quadrilinear nanodomains in the flagella of developing spermatids, whereas it is dispensable for functional channel assembly. CatSperτ interacts with ciliary trafficking machinery in a C2-dependent manner. These findings provide insights into the CatSper channel trafficking to the Ca2+ signaling nanodomains and the shared molecular mechanisms of ciliary and flagellar membrane targeting. •CatSperτ encoded by C2cd6 is a C2 membrane-associating domain-containing protein•CatSperτ loss of function impairs sperm hyperactivation and male fertility•CatSperτ adopts ciliary trafficking machineries for flagellar targeting via C2 domain•CatSperτ targets the CatSper channel into nanodomains of developing sperm flagella Hwang et al. report that the C2 domain protein CatSperτ targets the sperm CatSper Ca2+ channel to linear domains of the sperm flagellum during development. The findings provide fundamental insights into CatSper trafficking and the shared molecular mechanisms among ciliary and flagellar membrane targeting.
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AUTHOR CONTRIBUTIONS
J.-J.C. conceived and supervised the project. J.-J.C. and J.Y.H. designed, performed, and analyzed experiments. J.-J.C. and J.Y.H. generated CatSpert-mutant mice. Y.L. and M.I. created CatSpert-knockout mice. J.Y.H. performed molecular and cell biology experiments, including expression construct generation, virus particle production, IP, immunocytochemistry, confocal and SIM imaging, sperm motility analysis, IP mass spectrometry, and proteomics data analysis. H.W. did electrophysiological recordings. H.W. and J.Y.H. analyzed the electrophysiology data. Y.L. performed IVF and histology experiments. M.I. provided crucial reagents and materials. J.Y.H. assembled figures. J.Y.H. and J.-J.C. wrote the manuscript with input from the co-authors.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2021.110226