This presentation explores the role of the voltage-gated proton channel (HV1) in maintaining pH homeostasis in human cells and its implications in cancer biology. Elevated HV1 expression in malignant cells correlates with increased cell invasion and migration. We examined 197 somatic mutations in the HVCN1 gene, identifying key mutations that impact proton selectivity and voltage sensing. Notably, we discovered a mutation hotspot within the S4 transmembrane domain. Five specific mutations (R205W, R208W, R208Q, G215E, G215R) were further analyzed, revealing significant alterations in channel gating while preserving proton selectivity. These findings suggest that somatic mutations in HV1 can mimic the effects of HV1 inhibition on cancer cell behavior, highlighting their potential as therapeutic targets.
Zeitraum
21 Okt. 2024
Ereignistitel
Department of Physiology and Biophysics Seminar Series