An ion channel on steroids: the unconventional pathway of calcium regulation by endogenous cannabinoids
Polina Lishko, PhD
Assistant Professor of Cell and Developmental Biology
Department of Molecular and Cell Biology
Host: Sharona Gordon
Ion channels control sperm activity by regulating intracellular levels of calcium, which stimulates cell motility and fertility. Steroid hormone progesterone produced by an ovulated egg promotes the entry of calcium through sperm channel CatSper- an event so central for fertilization that men lacking these channels are infertile. We have demonstrated that human CatSper is associated with a membrane progesterone receptor, which makes human spermatozoa controlled by the female reproductive cycle. The identity of this receptor has been recently revealed to be serine hydrolase ABHD2 that degrades endogenous CatSper inhibitor 2-arachidonoylglycerol upon progesterone exposure. ABHD2 is ubiquitously expressed, and the pathway we have discovered in spermatozoa, is likely a universal pathway that defines membrane steroid signaling in other tissues.