CatSper: A Unique Calcium Channel of the Sperm Flagellum

Abstract

To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile. This calcium channel is regulated by various endogenous compounds, such as steroids, prostaglandins, endocannabinoids, and intracellular pH. Being a sperm-specific ion channel that is not expressed anywhere else in the body, CatSper represents an ideal target for the development of female and even male contraceptives. In this review, we discuss the recent advances in studying CatSper functional properties and discuss future steps that are required to take in order to achieve a deep understanding of the molecular basis of CatSper function.

Keywords: CatSper; Spermatozoa; flagellum; sperm ion channels.

Figure 1. Ion channels of the human sperm flagellum

Schematic representation of a human spermatozoon with cellular compartments and distribution of ion channels found along the principal piece: CatSper, calcium channel; Hv1, voltage-gated proton channel; Slo1/Slo3, potassium channels; the identity of a Na⁺ channel or transporter is yet to be characterized.