Abstract
Ion channels control sperm navigation within the female reproductive tract and, thus, are critical for their ability to find and fertilize an egg. The flagellar calcium channel CatSper controls sperm hyperactivated motility and is dependent on an alkaline cytoplasmic pH. The latter is accomplished by either proton transporters or, in human sperm, via the voltage-gated proton channel Hv1. To provide concerted regulation, ion channels and their regulatory proteins must be compartmentalized. Here, we describe flagellar regulatory nanodomains comprised of Hv1, CatSper, and its regulatory protein ABHD2. Super-resolution microscopy revealed that Hv1 is distributed asymmetrically within bilateral longitudinal lines and that inhibition of this channel leads to a decrease in sperm rotation along the long axis. We suggest that specific distribution of flagellar nanodomains provides a structural basis for the selective activation of CatSper and subsequent flagellar rotation. The latter, together with hyperactivated motility, enhances the fertility of sperm.
Highlights
Fast ciliary responses rely on efficient signal transduction
The members of the transduction cascade are tightly compartmentalized into regulatory nanodomains that are located in close proximity (Burns and Pugh, 2010)
Hv1 Forms Bilateral Lines that Run the Entire Length of the Principal Piece The sperm principal piece (PP) is a distinct flagellar compartment comprising the majority of the flagellar length that contains the fibrous sheath, a submembrane scaffold structure to which membrane proteins are docked (Eddy et al, 2003; Inaba, 2011; Figures 1A and 1B)
Summary
Fast ciliary responses rely on efficient signal transduction. To achieve rapid signaling, the members of the transduction cascade are tightly compartmentalized into regulatory nanodomains that are located in close proximity (Burns and Pugh, 2010). As mammalian sperm ascend in the oviduct, they have to overcome upstream fluid flow To succeed in such a task, spermatozoa engage in rheotaxis (Kantsler et al, 2014; Miki and Clapham, 2013) and display specific flagellar motility patterns: hyperactivation and rotation of the flagellum around its longitudinal axis (Ishijima et al, 1992). The resulting Ca2+ influx directly affects axonemal function and triggers hyperactivation and, perhaps, rotation Both motility patterns are required for sperm to detach from the oviductal epithelia (Babcock et al, 2014; Carlson et al, 2005; Ho et al, 2002; Miki and Clapham, 2013), their precise regulatory mechanisms have not been identified. We investigated whether the spatio-functional regulation of sperm Hv1, CatSper, and its regulatory protein
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