title: Post-translational cleavage of Hv1 in human sperm tunes pH- and voltage-dependent gating.
abstract: In human sperm, proton flux across the membrane is controlled by the voltage-gated proton channel Hv1. We show that sperm harbour both Hv1 and an N-terminally cleaved isoform termed Hv1Sper. The pH-control of Hv1Sper and Hv1 is distinctively different. Hv1Sper and Hv1 can form heterodimers that combine features of both constituents. Cleavage and heterodimerization of Hv1 might represent an adaptation to the specific requirements of pH control in sperm.
  
  
  
  In human sperm, the voltage-gated proton channel Hv1 controls the flux of protons across the flagellar membrane. Here, we show that sperm harbour Hv1 and a shorter isoform, termed Hv1Sper. Hv1Sper is generated from Hv1 by removal of 68 amino acids from the N-terminus by post-translational proteolytic cleavage. The pH-dependent gating of the channel isoforms is distinctly different. In both Hv1 and Hv1Sper, the conductance-voltage relationship is determined by the pH difference across the membrane (∆pH). However, simultaneous changes in intracellular and extracellular pH that leave ΔpH constant strongly shift the activation curve of Hv1Sper but not that of Hv1, demonstrating that cleavage of the N-terminus tunes pH sensing in Hv1. Moreover, we show that Hv1 and Hv1Sper assemble as heterodimers that combine features of both constituents. We suggest that cleavage and heterodimerization of Hv1 represents an adaptation to the specific requirements of pH control in sperm.
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Thomas K
authors.identifier: 0000-0001-9358-1315
authors.initials: TK
authors.lastname: Berger
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Fußhöller
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Normann
authors.initials: N
authors.lastname: Goodwin
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bönigk
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Müller
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Nasim
authors.initials: N
authors.lastname: Dokani Khesroshahi
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.|Center of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenker
authors.affiliation: Max-Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wachten
authors.affiliation: Leibniz-Institute for Molecular Pharmacology, Berlin, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: U Benjamin
authors.initials: UB
authors.lastname: Kaupp
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.|Center of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Strünker
mesh_terms: D000818:Animals; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020545:Respiratory Mucosa; D057057:Serine Proteases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: C510235:HVCN1 protein, human; D007473:Ion Channels; D015842:Serine Proteinase Inhibitors; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D057057:Serine Proteases
keywords: electrophysiology; ion channels; sperm; voltage-gated channels