HAP1 overexpression reduced the surface expression and attenuated KCNQ4-mediated potassium current, indicating it acts as a negative regulator of KCNQ4.
HAP1 acts as a negative regulator of KCNQ4 by reducing its surface expression and attenuating potassium currents, highlighting a potential target for maintaining channel stability in hearing loss.
Absolute Event Rate: 0% vs 0%
The voltage-gated channel subfamily Q member 4 (KCNQ4), a K+ channel, is one of the most frequently mutated genes in autosomal dominant non-syndromic hearing loss. KCNQ4, which contains six transmembrane domains and a long cytoplasmic C-terminal tail, plays a crucial role in K+ recycling in the inner ear. Although KCNQ4 binds to various interactors, specific binding sites of the interactors remain elusive, and the biological significance of these interactions remains unknown. Therefore, this study aimed to discover a novel interactor of KCNQ4 and delineate its functional role in KCNQ4 regulation. We discovered a novel interactor of KCNQ4, huntingtin-associated protein 1 (HAP1), in addition to calmodulin, which interacts with the C-terminus of KCNQ4 using a yeast two-hybrid assay. This interaction requires the B-segment of KCNQ4 as demonstrated by protein domain analysis. A thorough investigation of the biochemical and physiological consequences of this association revealed that HAP1 overexpression reduced surface expression and attenuated the potassium current mediated by KCNQ4. This suggests that HAP1 acts as a negative regulator of KCNQ4, potentially through the disruption of normal endocytic trafficking. These findings enhance the understanding of KCNQ4 regulation at the molecular level and highlight the potential of the HAP1-KCNQ4 axis as a target for interventions aimed at maintaining channel surface stability.
Kim et al. (Thu,) reported a other. HAP1 overexpression reduced the surface expression and attenuated KCNQ4-mediated potassium current, indicating it acts as a negative regulator of KCNQ4.