ArticleNature communications2021
Direct activation of the proton channel by albumin leads to human sperm capacitation and sustained release of inflammatory mediators by neutrophils.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- A designer pore-blocking peptide reveals an electrostatic complementation mechanism for the inhibition-resistant Kv1.5 channel.Science advances · 2026Article
- Early Origin of the Human Seminal Plasma Proteome During Vertebrate Evolution.Genome biology and evolution · 2026Article
- Amyloid precursor protein is a subunit of microglial Hv1 channels.Current opinion in immunology · 2026Review
- Bicarbonate buffer enhances functional sperm selection compared to Zwitterionic buffers in sperm preparation.Scientific reports · 2026Article
- Zhenwu decoction ameliorates adriamycin-induced nephrotic syndrome in rats via dual modulation of AVP-V2R-AQP2 and RAAS-MR-AQP3 pathways.Renal failure · 2025Article
- C6 peptide blockade of Hv1 channels inhibits neutrophil migration into the lungs to suppress Pseudomonas aeruginosa-induced acute lung injury.Respiratory research · 2025Article
- Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Expression and Purification of the Human Voltage-Gated Proton Channel (hHBio-protocol · 2025Article
- Bovine serum albumin-induced calcium influx triggers soluble adenylyl cyclase activation and cyclic AMP signalling pathways in mouse sperm capacitation.The Journal of physiology · 2025Article
- Validation of HvFrontiers in cellular neuroscience · 2025Article
- The neutrophil percentage-to-albumin ratio is an independent risk factor for poor prognosis in peritoneal dialysis patients.Renal failure · 2024Article
- Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis.JHEP reports : innovation in hepatology · 2024Article
- Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization.Biomolecules · 2024Review
- Review
- High-concentration bovine serum albumin enhances fertilization ability of cold-stored rat sperm.The Journal of reproduction and development · 2024Article
- MicroRNAs and Their Associated Genes Regulating the Acrosome Reaction in Sperm of High- versus Low-Fertility Holstein Bulls.Animals : an open access journal from MDPI · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- The sperm-specific KFrontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Human voltage-gated proton channels (hHv1) extrude protons from cells to compensate for charge and osmotic imbalances due metabolism, normalizing intracellular pH and regulating protein function. Human albumin (Alb), present at various levels throughout the body, regulates oncotic pressure and transports ligands. Here, we report Alb is required to activate hHv1 in sperm and neutrophils. Dose-response studies reveal the concentration of Alb in semen is too low to activate hHv1 in sperm whereas the higher level in uterine fluid yields proton efflux, allowing capacitation, the acrosomal reaction, and oocyte fertilization. Likewise, Alb activation of hHv1 in neutrophils is required to sustain production and release of reactive oxygen species during the immune respiratory burst. One Alb binds to both voltage sensor domains (VSDs) in hHv1, enhancing open probability and increasing proton current. A computational model of the Alb-hHv1 complex, validated by experiments, identifies two sites in Alb domain II that interact with the VSDs, suggesting an electrostatic gating modification mechanism favoring the active "up" sensor conformation. This report shows how sperm are triggered to fertilize, resolving how hHv1 opens at negative membrane potentials in sperm, and describes a role for Alb in physiology that will operate in the many tissues expressing hHv1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.