HVCN1 Membrane Protein Introduction

Introduction of HVCN1

HVCN1, encoded by HVCN1 gene, is a voltage-gated proton-selective channel. The encoded protein has 273 amino acids. The topology analysis has shown that HVCN1 contains a conserved voltage-sensing domain (VSD) consisting of four transmembrane segments (S1-S4). Unlike other voltage-gated ion channels, HVCN1 lacks a pore domains S5-S6. Hence, the proton permeation feature is only determined by the VSD of HVCN1. In mammals and many other species, HVCN1 forms a dimer on the cell membrane.

Function of HVCN1 Membrane Protein

HVCN1 functions as a selective proton channel that mediates the proton permeability of membranes in accordance with the electrochemical gradient. HVCN1 has been reported to be highly expressed in certain cells of the immune system where it is involved in host defenses. HVCN1 protein is required for the acute production of reactive oxygen species (ROS) in phagocytosis, and antibody production in B cells. It has been revealed that neutrophils of HVCN1 deficiency produce less ROS than neutrophils from WT mice during phagocyte respiratory burst. And HVCN1 deficiency in B cells will decrease antibody response. Furthermore, HVCN1 has been suggested to play a role in the development of diabetes via regulating insulin secretion and promoting ROS production in β-cells. HVCN1 knockdown significantly decreases glucose and K⁺ induced insulin secretion in β-cells and intracellular Ca²⁺ homeostasis. In addition, HVCN1-mediated H⁺ efflux is also involved in the capacitation in human sperm, histamine release by basophil, an alkaline airway surface liquid acidification, and the development of several cancers.

Fig.1 Schematic representation of NADPH oxidase and HVCN1 function in phagocytes. (Capasso, 2011)

Application of HVCN1 Membrane Protein in Literature

1. Asuaje A., et al. Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs. Channels. 2018, 12(1): 58-64. PubMed ID: 28514187
   
   

   The study shows that diphenhydramine, the histamine H1-receptor antagonist, can suppress Hv1-mediated currents and result in the decrease of intracellular pH and cellular viability in leukemia.

2. Kawai T., et al. Unconventional role of voltage-gated proton channels (VSOP/Hv1) in regulation of microglial ROS production. Journal of Neurochemistry. 2017, 142(5): 686-699. PubMed ID: 28628214
   
   

   The study shows that ROS production regulated by VSOP/Hv1 is complex in microglia. The extracellular ROS production in Hv1-deficient neutrophils of mice is lower than WT mice. However, ROS production in isolated Hv1-deficient microglia is higher than the cells from WT mice. Additionally, VSOP/Hv1 in microglial ROS production depends on age.

3. Yu Y., et al. Hv1 proton channel facilitates production of ROS and pro-inflammatory cytokines in microglia and enhances oligodendrocyte progenitor cells damage from oxygen-glucose deprivation in vitro. Biochemical & Biophysical Research Communications. 2018, 498(1): 1-8. PubMed ID: 28676401
   
   

   The study indicates that Hv1 deficiency has a protective effect on oligodendrocyte precursor cell (OPC) through inhibiting ROS and pro-inflammatory cytokine production in microglia. Hence, microglial Hv1 can be regarded as a potential therapeutic target for periventricular leukomalacia.

4. Kawai T., et al. Mechanistic insight into the suppression of microglial ROS production by voltage-gated proton channels (VSOP/Hv1). Channels. 2018, 12(1): 1-8. PubMed ID: 28961043
   
   

   The conventional study reports that VSOP/Hv1 can enhance ROS production in immune cells. However, this study indicates an unconventional regulatory mechanism of ROS production by VSOP/Hv1 in microglia.

5. Wang X., et al. Deficiency of voltage-gated proton channel Hv1 attenuates streptozotocin-induced β-cell damage. Biochemical & Biophysical Research Communications. 2018, 498(4): 975-980. PubMed ID: 29550486
   
   

   The study shows that Hv1 deficiency significantly relieves streptozotocin-induced β-cell damage and ROS production in pancreatic β-cells, suggesting the role of Hv1 in development of diabetes.

HVCN1 Preparation Options

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Reference

1. Capasso M, et al. (2011). pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1. Trends in Cell Biology. 21(1): 20-28.

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