Wobig, Lea: Characterization of the hyperpolarization-activated, highly-selective proton channel HCNL1 found in the sperm of the zebrafish Danio rerio. - Bonn, 2021. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-61821
@phdthesis{handle:20.500.11811/9055,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-61821,
author = {{Lea Wobig}},
title = {Characterization of the hyperpolarization-activated, highly-selective proton channel HCNL1 found in the sperm of the zebrafish Danio rerio},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2021,
month = apr,

note = {Zebrafish are external fertilizers and release their gametes into the surrounding water. Yet, the freshwater environment with its low osmolarity poses a challenge for the gametes. Given these unique ion conditions, it seems likely that zebrafish sperm have evolved specialized ion channels that are adapted to the freshwater environment. However, very little is known about the sperm of freshwater fish.
Another field that is still poorly understood is that of proton channels. Proton channels are exceptional among ion channels. Since protons differ substantially from other ions in their properties, their permeation pathways are very different from those of other ion channels. Proton channels select protons against other ions that are up to a million-fold more abundant, and only a few have been identified so far.
In my PhD thesis, I characterized a novel proton channel that belongs to the HCN channel family and is found in zebrafish sperm (drHCNL1). Despite its overall similarity to classical HCN channels that conduct K+ and Na+, drHCNL1 is exquisitely selective for protons. Activated by hyperpolarization, it conducts protons into the cytosol under physiological conditions, whereas the only other known voltage-gated proton channel, Hv1, is activated by depolarization and expels protons from the cell. Remarkably, protons permeate through drHCNL1’s voltage-sensing domain, whereas the “classical” pore domain is non-functional. Crucial for this proton permeation pathway is a methionine residue, which interrupts the series of regularly spaced arginine residues in the S4 voltage sensor. DrHCNL1 forms a tetramer and thus contains four proton pores. In contrast to classical HCN channels, drHCNL1 is not modulated by cyclic nucleotides. Another ion channel in zebrafish sperm previously identified, drCNGK, is also insensitive to cyclic nucleotides and, instead, is controlled by intracellular pH. My results suggest that both channels are functionally related, and that protons rather than cyclic nucleotides serve as cellular messengers in zebrafish sperm. The primary function of HCN channels is to depolarize the cell after hyperpolarization. In freshwater that is extremely low in Na+, a channel conducting Na+ would hyperpolarize sperm even further. Through small modifications in two key functional domains, drHCNL1 has been transformed to a proton-selective channel and thus evolutionarily adapted to the freshwater environment so that the sperm’s ability to depolarize is conserved.},

url = {http://hdl.handle.net/20.500.11811/9055}
}

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