Details

Autor(en) / Beteiligte

• Hwang, Jae Yeon
• Mannowetz, Nadja
• Zhang, Yongdeng
• Everley, Robert A.
• Gygi, Steven P.
• Bewersdorf, Joerg
• Lishko, Polina V.
• Chung, Jean-Ju

Titel

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

Ist Teil von

• Cell, 2019-05, Vol.177 (6), p.1480-1494.e19

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •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 A pH-dependent calcium sensor enables modulation of sperm motility in response to changing conditions along the female reproductive tract.