A01:Regulatory function of zinc in sperm physiology
Takafumi KAWAI
(Graduate School of Medicine, Osaka university)
Lab website

Zinc is a trace mineral, but vital for maintaining the health of our bodies. Zinc plays important roles in keeping the function of a variety of proteins, including “ion channels” which we have mainly investigated. Zinc can affect the ion channel function either at extracellular or intracellular side, and we have investigated the high-zinc sensitive ion channel “voltage-gated proton channel”. We found that the zinc-sensitivity of voltage-gated proton channel is not conserved through vertebrates; voltage-gated proton channel of most vertebrates other than mammals is rather resistant to zinc. Interestingly, such difference in zinc sensitivity appears to have negative correlation with the serum zinc level (Adisorn et al., 2017). This result raises the possibility that zinc sensitivity of voltage-gated proton channel was acquired in accordance with a change in the serum zinc concentration, and this study highlights the biological variation and importance of voltage-gated proton channel in different animal species. In the current project, we want to start the study about zinc modulation of ion channels that is more related to the biological function. Especially, sperm, which also express Hv1, is known to contain high amount of zinc, indicating its essential function for fertilization. However, the exact machinery underlying it is still elusive. So, we will elucidate this important mechanism.

Major publications
Kawai T, Miyata H, Nakanishi H, Sakata S, Morioka S, Sasaki J, Watanabe M, Sakimura K, Fujimoto T, Sasaki T, Ikawa M, Okamura Y.
“Polarized PtdIns(4,5)P2 distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility.”
Proc. Natl. Acad. Sci. U. S. A. 2019, 116(51), 26020-26028
doi: 10.1073/pnas.1916867116.
Kawai T, Okochi Y, Ozaki T, Imura Y, Koizumi S, Yamazaki M, Abe M, Sakimura K, Yamashita T, Okamura Y
“Unconventional role of voltage-gated proton channels (VSOP/Hv1) in regulation of microglial ROS production.”
J. Neurochem. 2017, 142(5), 686-699
doi: 10.1111/jnc.14106.
Ratanayotha A, Kawai T*, Higashijima S, Okamura Y
“Molecular and functional characterization of the voltage-gated proton channel in zebrafish neutrophils”
Physiol. Reports. 2017, 5(15), e133345
doi: 10.14814/phy2.13345.
