Cell
Volume 177, Issue 6, 30 May 2019, Pages 1480-1494.e19
Journal home page for Cell

Article
Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility

https://doi.org/10.1016/j.cell.2019.03.047Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Efcab9 encodes an evolutionarily conserved, sperm-specific EF-hand domain protein

  • Efcab9-deficient mice have sperm motility defects and compromised male fertility

  • EFCAB9 senses both pH and Ca2+ helping regulate flagellar CatSper channel activity

Summary

Varying pH of luminal fluid along the female reproductive tract is a physiological cue that modulates sperm motility. CatSper is a sperm-specific, pH-sensitive calcium channel essential for hyperactivated motility and male fertility. Multi-subunit CatSper channel complexes organize linear Ca2+ signaling nanodomains along the sperm tail. Here, we identify EF-hand calcium-binding domain-containing protein 9 (EFCAB9) as a bifunctional, cytoplasmic machine modulating the channel activity and the domain organization of CatSper. Knockout mice studies demonstrate that EFCAB9, in complex with the CatSper subunit, CATSPERζ, is essential for pH-dependent and Ca2+-sensitive activation of the CatSper channel. In the absence of EFCAB9, sperm motility and fertility is compromised, and the linear arrangement of the Ca2+ signaling domains is disrupted. EFCAB9 interacts directly with CATSPERζ in a Ca2+-dependent manner and dissociates at elevated pH. These observations suggest that EFCAB9 is a long-sought, intracellular, pH-dependent Ca2+ sensor that triggers changes in sperm motility.

Keywords

sperm motility
male fertility
Ca2+ channel
CatSper
pH sensing
Ca2+ sensor
Ca2+ signal transduction

Cited by (0)

6

Lead Contact