The Non-Gastric H+/K+ ATPase (ATP12A) Is Expressed in Mammalian Spermatozoa

Abstract

H+/K+ ATPase Type 2 is an heteromeric membrane protein involved in cation transmembrane transport and consists of two subunits: a specific α subunit (ATP12A) and a non-specific β subunit. The aim of this study was to demonstrate the presence and establish the localization of ATP12A in spermatozoa from Bubalus bubalis, Bos taurus and Ovis aries. Immunoblotting revealed, in all three species, a major band (100 kDa) corresponding to the expected molecular mass. The ATP12A immunolocalization pattern showed, consistently in the three species, a strong signal at the acrosome. These results, described here for the first time in spermatozoa, are consistent with those observed for the β1 subunit of Na+/K+ ATPase, suggesting that the latter may assemble with the α subunit to produce a functional ATP12A dimer in sperm cells. The above scenario appeared to be nicely supported by 3D comparative modeling and interaction energy calculations. The expression of ATP12A during different stages of bovine sperm maturation progressively increased, moving from epididymis to deferent ducts. Based on overall results, we hypothesize that ATP12A may play a role in acrosome reactions. Further studies will be required in order to address the functional role of this target protein in sperm physiology.

A Genome-Wide Association Study for Resistance to Tropical Theileriosis in Two Bovine Portuguese Autochthonous Breeds

“…In addition, we identified genes potentially associated with resistance to Theileriosis in Alentejana breed animals that appear to have significant productive importance, such as the ATP12A (ATPase H/K transporting non-gastric alpha2 subunit), SHISA9 (shisa family member 9), and FSTL5 (follistatin-like 5) genes. The ATP12A gene encodes the H+/K+ ATPase type 2 protein, a membrane protein involved in transmembrane cation transport, which is present in sperm and acts in the acrosome reaction at fertilization [51]. On the other hand, the SHISA9 gene is associated with pre-weaning growth, while the FSTL5 gene appears to be associated with muscle hypertrophy in cattle, inducing follistatin to increase insulin action at the skeletal muscle level [52][53][54][55].…”

Analysis of 206 whole‐genome resequencing reveals selection signatures associated with breed‐specific traits in Hu sheep

“…SOX18 was more strongly expressed in spermatogonial cells and spermatocytes than in spermatids and testicular somatic cells of sheep (Yang et al., 2021 ). ATP12A played a role in acrosome reactions (Favia et al., 2022 ). BCL2L11 affected sperm apoptosis (Ding et al., 2021 ).…”

ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases

“…It has been found expressed in many epithelial tissues, including kidney, colon, skin, placenta, and prostate, where it is involved in acid-base and K + and Na + homeostasis [3][4][5][6]. It has also been observed in mammalian spermatozoa, where it may play a role in acrosome reactions [7]. Importantly, it is expressed in the respiratory tract, particularly on the apical membrane of mucus-secreting cells, both in the surface airway epithelia (goblet cells) and in the submucosal glands [8,9].…”