Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2017 Mar 01;5955:1533-1546. doi: 10.1113/JP273189.
Show Gene links
Show Anatomy links
Post-translational cleavage of Hv1 in human sperm tunes pH- and voltage-dependent gating.
Berger TK
,
Fußhöller DM
,
Goodwin N
,
Bönigk W
,
Müller A
,
Dokani Khesroshahi N
,
Brenker C
,
Wachten D
,
Krause E
,
Kaupp UB
,
Strünker T
.
???displayArticle.abstract???
KEY POINTS: 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.
ABSTRACT: 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.
AUSTIN,
Observations on the penetration of the sperm in the mammalian egg.
1951, Pubmed
AUSTIN,
Observations on the penetration of the sperm in the mammalian egg.
1951,
Pubmed
Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed
Batra-Safferling,
Glutamic acid-rich proteins of rod photoreceptors are natively unfolded.
2006,
Pubmed
Berger,
The pore of the voltage-gated proton channel.
2011,
Pubmed
,
Xenbase
Brenker,
The CatSper channel: a polymodal chemosensor in human sperm.
2012,
Pubmed
Brenker,
The Ca2+-activated K+ current of human sperm is mediated by Slo3.
2014,
Pubmed
Bönigk,
An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis.
2009,
Pubmed
CHANG,
Fertilizing capacity of spermatozoa deposited into the fallopian tubes.
1951,
Pubmed
Capasso,
HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.
2010,
Pubmed
Cherny,
Tryptophan 207 is crucial to the unique properties of the human voltage-gated proton channel, hHV1.
2015,
Pubmed
Cherny,
The voltage-activated hydrogen ion conductance in rat alveolar epithelial cells is determined by the pH gradient.
1995,
Pubmed
Chung,
Structurally distinct Ca(2+) signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility.
2014,
Pubmed
Dyson,
Intrinsically unstructured proteins and their functions.
2005,
Pubmed
El Chemaly,
VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification.
2010,
Pubmed
Gonzalez,
Strong cooperativity between subunits in voltage-gated proton channels.
2010,
Pubmed
Henderson,
The superoxide-generating NADPH oxidase of human neutrophils is electrogenic and associated with an H+ channel.
1987,
Pubmed
Hondares,
Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells.
2014,
Pubmed
Hong,
Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.
2013,
Pubmed
,
Xenbase
Iovannisci,
Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T.
2010,
Pubmed
Koch,
Multimeric nature of voltage-gated proton channels.
2008,
Pubmed
,
Xenbase
Lee,
Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1.
2008,
Pubmed
Linding,
GlobPlot: Exploring protein sequences for globularity and disorder.
2003,
Pubmed
Lishko,
Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel.
2010,
Pubmed
Molday,
The cGMP-gated channel of the rod photoreceptor cell characterization and orientation of the amino terminus.
1991,
Pubmed
,
Xenbase
Mony,
A specialized molecular motion opens the Hv1 voltage-gated proton channel.
2015,
Pubmed
Musset,
Aspartate 112 is the selectivity filter of the human voltage-gated proton channel.
2011,
Pubmed
Musset,
Detailed comparison of expressed and native voltage-gated proton channel currents.
2008,
Pubmed
Musset,
NOX5 in human spermatozoa: expression, function, and regulation.
2012,
Pubmed
Pathak,
The Hv1 proton channel responds to mechanical stimuli.
2016,
Pubmed
,
Xenbase
Ramsey,
A voltage-gated proton-selective channel lacking the pore domain.
2006,
Pubmed
Ramsey,
Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst.
2009,
Pubmed
Ramsey,
An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1.
2010,
Pubmed
Sasaki,
A voltage sensor-domain protein is a voltage-gated proton channel.
2006,
Pubmed
Strünker,
The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm.
2011,
Pubmed
Strünker,
A K+-selective cGMP-gated ion channel controls chemosensation of sperm.
2006,
Pubmed
Taylor,
A voltage-gated H+ channel underlying pH homeostasis in calcifying coccolithophores.
2011,
Pubmed
Tombola,
The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor.
2008,
Pubmed
,
Xenbase
Tombola,
The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity.
2010,
Pubmed
,
Xenbase
Visconti,
Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway.
1995,
Pubmed
Visconti,
Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation.
1995,
Pubmed
Wang,
Clinicopathological and biological significance of human voltage-gated proton channel Hv1 protein overexpression in breast cancer.
2012,
Pubmed
Wu,
The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.
2012,
Pubmed