A family of hyperpolarization-activated channels selective for protons

Wobig, Lea; Wolfenstetter, Thérèse; Fechner, Sylvia; Bönigk, Wolfgang; Körschen, Heinz Gerd; Jikeli, Jan; Trötschel, Christian; Feederle, Regina; Kaupp, Ulrich Benjamin; Seifert, Reinhard; Berger, Thomas Klaus

doi:10.1073/pnas.2001214117

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学術論文

A family of hyperpolarization-activated channels selective for protons

MPS-Authors

Wobig, Lea
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

Wolfenstetter, Thérèse
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Fechner, Sylvia
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Bönigk, Wolfgang
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Körschen, Heinz Gerd
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Jikeli, Jan
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Kaupp, Ulrich Benjamin
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182767

Seifert, Reinhard
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Berger, Thomas Klaus
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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https://www.pnas.org/content/early/2020/05/27/2001214117
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引用

Wobig, L., Wolfenstetter, T., Fechner, S., Bönigk, W., Körschen, H. G., Jikeli, J., Trötschel, C., Feederle, R., Kaupp, U. B., Seifert, R., & Berger, T. K. (2020). A family of hyperpolarization-activated channels selective for protons. Proceedings of the National Academy of Sciences of the United States of America, 117(24), 13783-13791. doi:10.1073/pnas.2001214117.

引用: https://hdl.handle.net/21.11116/0000-0006-7C87-7

要旨

Proton (H+) channels are special: They select protons against other ions that are up to a millionfold more abundant. Only a few proton channels have been identified so far. Here, we identify a family of voltage-gated “pacemaker” channels, HCNL1, that are exquisitely selective for protons. HCNL1 activates during hyperpolarization and conducts protons into the cytosol. Surprisingly, protons permeate through the channel’s voltage-sensing domain, whereas the pore domain is nonfunctional. Key to proton permeation is a methionine residue that interrupts the series of regularly spaced arginine residues in the S4 voltage sensor. HCNL1 forms a tetramer and thus contains four proton pores. Unlike classic HCN channels, HCNL1 is not gated by cyclic nucleotides. The channel is present in zebrafish sperm and carries a proton inward current that acidifies the cytosol. Our results suggest that protons rather than cyclic nucleotides serve as cellular messengers in zebrafish sperm. Through small modifications in two key functional domains, HCNL1 evolutionarily adapted to a low-Na+ freshwater environment to conserve sperm’s ability to depolarize.