Cell glycosaminoglycans content modulates human voltage‐gated proton channel (HV1) gating

Voltage‐gated proton channels (HV1) have been found in many mammalian cells and play a crucial role in the immune system, male fertility, and cancer progression. Glycosaminoglycans play a significant role in various aspects of cell physiology, including the modulation of membrane receptors and ion c...

Full description

Saved in:
Bibliographic Details
Published in:The FEBS journal 2022-05, Vol.289 (9), p.2593-2612
Main Authors: Orts, Diego J. B., Arcisio‐Miranda, Manoel
Format: Article
Language:English
Subjects:
Animals
Biosynthesis
Cell membranes
Channel gating
CHO Cells
Chondroitin sulfate
Chondroitin Sulfates
Cricetinae
Cricetulus
Dimers
Electric potential
Fertility
Fluidity
gating modulation
Glycosaminoglycans
gradient pH‐sensing
Heparan sulfate
Heparitin Sulfate
Humans
Immune system
Ion Channel Gating - physiology
Ion channels
Isoforms
Kinetics
Male
Mammalian cells
Membrane fluidity
Membranes
Protons
Receptor mechanisms
Sulfates
Viscosity
Voltage
voltage‐gated proton channels
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Voltage‐gated proton channels (HV1) have been found in many mammalian cells and play a crucial role in the immune system, male fertility, and cancer progression. Glycosaminoglycans play a significant role in various aspects of cell physiology, including the modulation of membrane receptors and ion channel function. We present here evidence that mechanosensitivity of the dimeric HV1 channel transduce changes on cell membrane fluidity related to the defective biosynthesis of chondroitin sulfate and heparan sulfate in Chinese Hamster Ovary (CHO‐745) cells into a leftward shift in the activation voltage dependence. This effect was accompanied by an increase in the H+ current, and an acceleration of the activation kinetics, under symmetrical or asymmetrical pH gradient (ΔpH) conditions. Similar gating alterations were evoked by two naturally occurring HV1 N‐terminal truncated isoforms expressed in wild‐type CHO‐K1 and CHO‐745 cells. On three different monomeric HV1 constructs, no alterations in the biophysical parameters were observed. Moreover, we have shown that HV1 gating can be modulated by manipulating CHO‐K1 cell membrane fluidity. Our results suggest that the defective biosynthesis of chondroitin sulfate and heparan sulfate on CHO‐745 cell increases membrane fluidity and allosterically modulates the coupling between voltage‐ and ΔpH‐sensing through the dimeric HV1 channel. Voltage‐gated proton channel conducts protons out of the cells, being important in cancer progression, male fertility, and neuronal death. We identified that the mechanosensitivity of the dimeric HV1 channel transduce changes on cell membrane fluidity related to the defective biosynthesis of GAGs in Chinese Hamster Ovary cells into a leftward shift in the activation voltage dependence and an increase in the H+ current under symmetrical or asymmetrical pH gradient conditions.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.16290