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Cell. 2014 May 8;157(4):808-22. doi: 10.1016/j.cell.2014.02.056.

Structurally distinct Ca(2+) signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility.

Author information

1
Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
2
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
3
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
4
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Department of Physics, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. Electronic address: zhuang@chemistry.harvard.edu.
5
Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: dclapham@enders.tch.harvard.edu.

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.

PMID:
24813608
PMCID:
PMC4032590
DOI:
10.1016/j.cell.2014.02.056
[Indexed for MEDLINE]
Free PMC Article
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