Cell glycosaminoglycans content modulates human voltage-gated proton channel (H(V)1) gating

Autor(es)

Orts, Diego J. B. ^[1] ; Arcisio-Miranda, Manoel ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Biofis, Lab Neurobiol Estrutural & Func LaNEF, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FEBS Journal; NOV 2021.
• Citações Web of Science: 0

Resumo

Voltage-gated proton channels (H(V)1) 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 H(V)1 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 (Delta pH) conditions. Similar gating alterations were evoked by two naturally occurring H(V)1 N-terminal truncated isoforms expressed in wild-type CHO-K1 and CHO-745 cells. On three different monomeric H(V)1 constructs, no alterations in the biophysical parameters were observed. Moreover, we have shown that H(V)1 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 Delta pH-sensing through the dimeric H(V)1 channel. (AU)

• Processo FAPESP: 16/17951-6 - OBSERVANDO O pH INTRACELULAR DE CÉLULAS DA MICRÓGLIA
• Beneficiário: Manoel de Arcisio Miranda Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/25204-9 - Validação de um modelo animal alternativo para o desenvolvimento de um sistema heterólogo de expressão de canais iônicos e receptores de membrana
• Beneficiário: Diego Jose Orts y Belato
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/13368-4 - Sistemas nanoestruturados: de modelos biomiméticos de membranas a carreadores de bioativos
• Beneficiário: Karin Do Amaral Riske
• Modalidade de apoio: Auxílio à Pesquisa - Temático