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 journalArticlepeer-review

183 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2014 May 8
Externally publishedYes

Bibliographical note

Funding Information:
We thank K. Miki and B. Navarro for discussions; L. Zhao, Y. Shang, and H. Warren for help with mice and western blots; and M. Ericsson and E. Benecchi at the Harvard Medical School EM facility for assistance with electron microscopy. This work was supported by NIH U01 HDO45857 (to D.E.C.) and by NIH 1R01 GM 068518 and 1R01 GM 096450 (to X.Z.).

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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