The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel K_V11.1 associated with long QT syndrome.

ABSTRACT: The voltage-gated potassium ion channel K_V11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause long QT syndrome (LQTS), which is associated with fatal arrhythmias. Approximately 90% of LQTS-associated variants cause intracellular protein transport (trafficking) dysfunction, which pharmacological chaperones like E-4031 can rescue. Protein folding and trafficking decisions are regulated by chaperones, protein quality control factors, and trafficking machinery comprising the cellular proteostasis network. Here, we test whether trafficking dysfunction is associated with alterations in the proteostasis network of pathogenic Kv11.1 variants and whether pharmacological chaperones can normalize the proteostasis network of responsi

SUBMITTER: Egly CL 

PROVIDER: S-EPMC11284683 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature