Platform: Ion Channels and Disease
2/18/2014 10:00:00 AM
REGULATION OF CATSPER CHANNEL THROUGH NON-CONVENTIONAL LIPID SIGNALING
Melissa R. Miller
, Yuriy Kirichok
, Polina Lishko
University of California, Berkeley, Berkeley, CA, USA,
Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
The sperm-specific cation channel, CatSper, regulates intracellular calcium levels and is crucial for male fertility, both in mice and humans. CatSper triggers hyperactivation, a type of inducible motility that enables sperm to penetrate the egg's protective vestments. For this motility change, human CatSper requires elevation of intracellular pH with simultaneous extracellular stimulation by progesterone which sperm encounter during their journey to the oocyte. In the absence of these stimuli, CatSper retains some basal activity which can be reversibly inhibited by mild lipid extraction. Here we report that basal CatSper activity, as recorded using whole-cell patch clamp technique from mature human spermatozoa, requires a lipid signaling molecule produced within the sperm plasma membrane. Furthermore, treatment with the female hormone progesterone up-regulates the production of this lipophilic signal. Development of a novel lipid extraction technique has provided a method for concentration, isolation, and identification of this lipid signaling molecule providing a better understanding of the lipidic pathways regulating male fertility in humans.
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