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https://www.readbyqxmd.com/read/27859356/posttranslational-cleavage-of-hv1-in-human-sperm-tunes-ph-and-voltage-dependent-gating
#1
Thomas K Berger, David M Fußhöller, Normann Goodwin, Wolfgang Bönigk, Astrid Müller, Nasim Dokani Khesroshahi, Christoph Brenker, Dagmar Wachten, Eberhard Krause, U Benjamin Kaupp, Timo Strünker
In human sperm, the voltage-gated proton channel Hv1 controls the flux of protons across the flagellar membrane. Here, we show that sperm harbor Hv1 and a shorter isoform, termed Hv1Sper. Hv1Sper is generated from Hv1 by removal of 68 amino acids from the N-terminus by posttranslational 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...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27801578/does-proton-conduction-in-the-voltage-gated-h-channel-hhv1-involve-grotthuss-like-hopping-via-acidic-residues
#2
Siri Camee van Keulen, Eleonora Gianti, Vincenzo Carnevale, Michael L Klein, Ursula Rothlisberger, Lucie Delemotte
Hv1 are ubiquitous highly selective voltage-gated proton channels involved in male fertility, immunology and the invasiveness of certain forms of breast cancer. The mechanism of proton extrusion in Hv1 is not yet understood while it constitutes the first step towards the design of high-affinity drugs aimed at this important pharmacological target. In this contribution, we explore the details of the mechanism via an integrative approach, using classical and QM/MM molecular dynamics simulations of a monomeric hHv1 model...
November 1, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27799320/the-hv1-proton-channel-responds-to-mechanical-stimuli
#3
Medha M Pathak, Truc Tran, Liang Hong, Béla Joós, Catherine E Morris, Francesco Tombola
The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27650914/a-mathematical-model-of-osteoclast-acidification-during-bone-resorption
#4
Frank V Marcoline, Yoichi Ishida, Joseph A Mindell, Smita Nayak, Michael Grabe
Bone resorption by osteoclasts occurs through the creation of a sealed extracellular compartment (ECC), or pit, adjacent to the bone that is subsequently acidified through a complex biological process. The low pH of the pit dissolves the bone mineral and activates acid proteases that further break down the bone matrix. There are many ion channels, transporters, and soluble proteins involved in osteoclast mediated resorption, and in the past few years, there has been an increased understanding of the identity and properties of some key proteins such as the ClC-7 Cl(-)/H(+) antiporter and the HV1 proton channel...
December 2016: Bone
https://www.readbyqxmd.com/read/27647906/molecular-mechanism-of-zn2-inhibition-of-a-voltage-gated-proton-channel
#5
Feng Qiu, Adam Chamberlin, Briana M Watkins, Alina Ionescu, Marta Elena Perez, Rene Barro-Soria, Carlos González, Sergei Y Noskov, H Peter Larsson
Voltage-gated proton (Hv1) channels are involved in many physiological processes, such as pH homeostasis and the innate immune response. Zn(2+) is an important physiological inhibitor of Hv1. Sperm cells are quiescent in the male reproductive system due to Zn(2+) inhibition of Hv1 channels, but become active once introduced into the low-Zn(2+)-concentration environment of the female reproductive tract. How Zn(2+) inhibits Hv1 is not completely understood. In this study, we use the voltage clamp fluorometry technique to identify the molecular mechanism of Zn(2+) inhibition of Hv1...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27637155/comparison-between-mouse-and-sea-urchin-orthologs-of-voltage-gated-proton-channel-suggests-role-of-s3-segment-in-activation-gating
#6
Souhei Sakata, Nana Miyawaki, Thomas J McCormack, Hiroki Arima, Akira Kawanabe, Nurdan Özkucur, Tatsuki Kurokawa, Yuka Jinno, Yuichiro Fujiwara, Yasushi Okamura
The voltage-gated proton channel, Hv1, is expressed in blood cells, airway epithelium, sperm and microglia, playing important roles in diverse biological contexts including phagocytosis or sperm maturation through its regulation of membrane potential and pH. The gene encoding Hv1, HVCN1, is widely found across many species and is also conserved in unicellular organisms such as algae or dinoflagellates where Hv1 plays role in calcification or bioluminescence. Voltage-gated proton channels exhibit a large variation of activation rate among different species...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27591540/dna-profile-of-dog-feces-as-evidence-to-solve-a-homicide
#7
L S Barrientos, J A Crespi, A Fameli, D M Posik, H Morales, P Peral García, G Giovambattista
Dog fecal samples were collected at the crime scene and from the shoes of the suspect to see whether they could be linked. DNA was genotyped using a 145bp fragment containing a 60bp hotspot region of the mitochondrial DNA (mtDNA) control region. Once the species origin was identified, sequences were aligned with the 23 canine haplotypes defined, showing that evidence and reference had 100% identity with haplotype 5. The frequency of haplotype 5 and the exclusion power of the reference population were 0.056 and 0...
September 2016: Legal Medicine
https://www.readbyqxmd.com/read/27572256/proton-currents-constrain-structural-models-of-voltage-sensor-activation
#8
Aaron L Randolph, Younes Mokrab, Ashley L Bennett, Mark Sp Sansom, Ian Scott Ramsey
The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H(+) conductance (GAQ). Mutation of a highly conserved 'gating charge' residue in the S4 helix (R1H) confers a resting-state H(+) 'shuttle' conductance (GSH) in VGCs and Ci VSP, and we now report that R1H is sufficient to reconstitute GSH in Hv1 without abrogating GAQ. Second-site mutations in S3 (D185A/H) and S4 (N4R) experimentally separate GSH and GAQ gating, which report thermodynamically distinct initial and final steps, respectively, in the Hv1 activation pathway...
August 30, 2016: ELife
https://www.readbyqxmd.com/read/27470181/deficiency-in-the-voltage-gated-proton-channel-hv1-increases-m2-polarization-of-microglia-and-attenuates-brain-damage-from-photothrombotic-ischemic-stroke
#9
Dai-Shi Tian, Chun-Yu Li, Chuan Qin, Madhuvika Murugan, Long-Jun Wu, Jun-Li Liu
Microglia become activated during cerebral ischemia and exert pro-inflammatory or anti-inflammatory role dependent of microglial polarization. NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in microglia plays an important role in neuronal damage after ischemic stroke. Recently, NOX and ROS are consistently reported to participate in the microglial activation and polarization; NOX2 inhibition or suppression of ROS production are shown to shift the microglial polarization from M1 toward M2 state after stroke...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27260771/pharmacological-modulation-of-proton-channel-hv1-in-cancer-therapy-future-perspectives
#10
Audry Fernández, Amaury Pupo, Karel Mena-Ulecia, Carlos Gonzalez
The pharmacological modulation of the immunosuppressive tumor microenvironment has emerged as a relevant component for cancer therapy. Several approaches aiming to deplete innate and adaptive suppressive populations, to circumvent the impairment in antigen presentation, and to ultimately increase the frequency of activated tumor-specific T cells are currently being explored. In this review, we address the potentiality of targeting the voltage-gated proton channel, Hv1, as a novel strategy to modulate the tumor microenvironment...
September 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27225904/voltage-gated-proton-channel-in-human-glioblastoma-multiforme-cells
#11
Luisa Ribeiro-Silva, Fernanda Oliveira Queiroz, Annielle Mendes Brito da Silva, Aparecida Emiko Hirata, Manoel Arcisio-Miranda
Solid tumors tend to have a more glycolytic metabolism leading to an accumulation of acidic metabolites in their cytosol, and consequently, their intracellular pH (pHi) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (HV1) can regulate the pHi in several cancers. Here we report the functional expression of voltage gated proton channels in a human glioblastoma multiforme (GBM) cell line, the most common and lethal brain tumor...
July 20, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/26954225/genetic-diversity-and-effect-of-selection-at-the-mitochondrial-hypervariable-region-in-major-nigerian-indigenous-goat-breeds
#12
Abdulhakeem Biola Ajibike, Babatunde Moses Ilori, Esther Oludayo Awotunde, Adeoye Ridwan Adegboyega, Ajoke Damilola Osinbowale, Matha N Bemji, Samuel Olutunde Durosaro, Ayotunde Oluwatumininu Adebambo
Mitochondrial DNA (mtDNA) hypervariable region 1 ( HV1) sequences of three Nigerian indigenous goat breeds; West African Dwarf (WAD), Red Sokoto (RS) and Sahel were used to investigate the genetic diversity and effect of selection between and among these populations. Deoxyribonucleic acid (DNA) of Nigerian indigenous chicken was extracted from blood samples collected and preserved on Fast Technology for Analysis (FTA) paper. The extracted DNA were amplified and sequenced with predefined mitochondria (mtDNA) primer sets for HV1...
January 18, 2016: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/26880249/ighv1-69-polymorphism-modulates-anti-influenza-antibody-repertoires-correlates-with-ighv-utilization-shifts-and-varies-by-ethnicity
#13
Yuval Avnir, Corey T Watson, Jacob Glanville, Eric C Peterson, Aimee S Tallarico, Andrew S Bennett, Kun Qin, Ying Fu, Chiung-Yu Huang, John H Beigel, Felix Breden, Quan Zhu, Wayne A Marasco
IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity...
February 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26843580/proton-channels-and-renal-hypertensive-injury-a-key-piece-of-the-dahl-salt-sensitive-rat-puzzle
#14
REVIEW
Paul M O'Connor, Avirup Guha, Carly A Stilphen, Jingping Sun, Chunhua Jin
Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury...
April 15, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/26809792/currents-through-hv1-channels-deplete-protons-in-their-vicinity
#15
Víctor De-la-Rosa, Esteban Suárez-Delgado, Gisela E Rangel-Yescas, León D Islas
Proton channels have evolved to provide a pH regulatory mechanism, affording the extrusion of protons from the cytoplasm at all membrane potentials. Previous evidence has suggested that channel-mediated acid extrusion could significantly change the local concentration of protons in the vicinity of the channel. In this work, we directly measure the proton depletion caused by activation of Hv1 proton channels using patch-clamp fluorometry recordings from channels labeled with the Venus fluorescent protein at intracellular domains...
February 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/26791748/signature-and-pathophysiology-of-non-canonical-pores-in-voltage-dependent-cation-channels
#16
Katharina Held, Thomas Voets, Joris Vriens
Opening and closing of voltage-gated cation channels allows the regulated flow of cations such as Na(+), K(+), and Ca(2+) across cell membranes, which steers essential physiological processes including shaping of action potentials and triggering Ca(2+)-dependent processes. Classical textbooks describe the voltage-gated cation channels as membrane proteins with a single, central aqueous pore. In recent years, however, evidence has accumulated for the existence of additional ion permeation pathways in this group of cation channels, distinct from the central pore, which here we collectively name non-canonical pores...
2016: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/26679583/draft-genome-sequence-of-pedobacter-sp-strain-hv1-an-isolate-from-medicinal-leech-mucosal-castings
#17
Brittany M Ott, Lidia Beka, Joerg Graf, Rita V M Rio
The Pedobacter sp. Hv1 strain was isolated from the medicinal leech, Hirudo verbana, mucosal castings. These mucosal sheds have been demonstrated to play a role in horizontal symbiont transmission. Here, we report the draft 4.9 Mbp genome sequence of Pedobacter sp. strain Hv1.
December 17, 2015: Genome Announcements
https://www.readbyqxmd.com/read/26559003/the-voltage-gated-proton-channel-hv1-is-expressed-in-pancreatic-islet-%C3%AE-cells-and-regulates-insulin-secretion
#18
Qing Zhao, Yongzhe Che, Qiang Li, Shangrong Zhang, Ying-Tang Gao, Yifan Wang, Xudong Wang, Wang Xi, Weiyan Zuo, Shu Jie Li
The voltage-gated proton channel Hv1 is a potent acid extruder that participates in the extrusion of the intracellular acid. Here, we showed for the first time, Hv1 is highly expressed in mouse and human pancreatic islet β-cells, as well as β-cell lines. Imaging studies demonstrated that Hv1 resides in insulin-containing granules in β-cells. Knockdown of Hv1 with RNA interference significantly reduces glucose- and K(+)-induced insulin secretion in isolated islets and INS-1 (832/13) β-cells and has an impairment on glucose- and K(+)-induced intracellular Ca(2+) homeostasis...
December 25, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26545175/single-nucleotide-polymorphisms-in-the-d-loop-region-of-mitochondrial-dna-is-associated-with-colorectal-cancer-outcome
#19
Cuiju Wang, Shengnan Zhao, Yanming Du, Zhanjun Guo
Single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with the risk and outcome in many cancers. We have identified risk associated D-loop SNPs for colorectal cancer previously, in the present study, we evaluate their prognostic value for postoperative survival of colorectal cancer (CRC). The minor haplotype of nucleotides 16290T and frequent haplotype of nucleotide 16298T in the hypervariable segment 1 (HV1) region of the D-loop were identified for their association with high survival rate of CRC...
November 6, 2015: Mitochondrial DNA
https://www.readbyqxmd.com/read/26458876/tryptophan-207-is-crucial-to-the-unique-properties-of-the-human-voltage-gated-proton-channel-hhv1
#20
Vladimir V Cherny, Deri Morgan, Boris Musset, Gustavo Chaves, Susan M E Smith, Thomas E DeCoursey
Part of the "signature sequence" that defines the voltage-gated proton channel (H(V1)) is a tryptophan residue adjacent to the second Arg in the S4 transmembrane helix: RxWRxxR, which is perfectly conserved in all high confidence H(V1) genes. Replacing Trp207 in human HV1 (hH(V1)) with Ala, Ser, or Phe facilitated gating, accelerating channel opening by 100-fold, and closing by 30-fold. Mutant channels opened at more negative voltages than wild-type (WT) channels, indicating that in WT channels, Trp favors a closed state...
November 2015: Journal of General Physiology
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