Structurally distinct Ca2+ signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility

Jean Ju Chung, Sang-Hee Shim, Robert A. Everley, Steven P. Gygi, Xiaowei Zhuang, David E. Clapham

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Spermatozoa must leave one organism, navigate long distances, and deliver their paternal DNA into a mature egg. For successful navigation and delivery, a sperm-specific calcium channel is activated in the mammalian flagellum. The genes encoding this channel (CatSpers) appear first in ancient uniflagellates, suggesting that sperm use adaptive strategies developed long ago for single-cell navigation. Here, using genetics, super-resolution fluorescence microscopy, and phosphoproteomics, we investigate the CatSper-dependent mechanisms underlying this flagellar switch. We find that the CatSper channel is required for four linear calcium domains that organize signaling proteins along the flagella. This unique structure focuses tyrosine phosphorylation in time and space as sperm acquire the capacity to fertilize. In heterogeneous sperm populations, we find unique molecular phenotypes, but only sperm with intact CatSper domains that organize time-dependent and spatially specific protein tyrosine phosphorylation successfully migrate. These findings illuminate flagellar adaptation, signal transduction cascade organization, and fertility. PaperFlick

Original languageEnglish
Pages (from-to)808-822
Number of pages15
JournalCell
Volume157
Issue number4
DOIs
Publication statusPublished - 2014 May 8
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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