TY - JOUR
T1 - Structurally distinct Ca2+ signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility
AU - Chung, Jean Ju
AU - Shim, Sang Hee
AU - Everley, Robert A.
AU - Gygi, Steven P.
AU - Zhuang, Xiaowei
AU - Clapham, David E.
N1 - 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.).
PY - 2014/5/8
Y1 - 2014/5/8
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84900327987&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.02.056
DO - 10.1016/j.cell.2014.02.056
M3 - Article
C2 - 24813608
AN - SCOPUS:84900327987
SN - 0092-8674
VL - 157
SP - 808
EP - 822
JO - Cell
JF - Cell
IS - 4
ER -