• Citer

A genetic variant of the sperm-specific SLO3 K(+) channel has altered pH and Ca(2+) sensitivities.

par Geng, Yanyan;Ferreira, Juan José́;Dzikunu, Victor;Butler, Alice;Lybaert, Pascale ;Yuan, Peng;Magleby, Karl KL;Salkoff, Lawrence;Santi, Celia CM
Référence The Journal of biological chemistry, 292, 21, page (8978-8987)
Publication Publié, 2017-05

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K(+)) channels and resultant K(+) efflux. Sperm-specific SLO3 K(+) channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K(+) conductance is both Ca(2+)- and pH i -sensitive. It has been debated whether Ca(2+)-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca(2+) sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca(2+) and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca(2+), the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca(2+) sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.