Dataset Information

T he proteostasis interactomes of trafficking - deficient K V 11.1 variants associated with Long QT Syndrome and pharmacological chaperone rescue

ABSTRACT: The voltage gated potassium ion channel KV11.1 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 can be rescued by pharmacological chaperones like E-4031. 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 responsive variants.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Early Embryonic Cell, Kidney

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Christian Egly

LAB HEAD: Lars Plate

PROVIDER: PXD050914 | Pride | 2024-08-10

REPOSITORIES: Pride

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			Action	DRS
	12Sept2023_CE_Exp4_16plex_0C_1.raw	Raw
	12Sept2023_CE_Exp4_16plex_100C_7.raw	Raw
	12Sept2023_CE_Exp4_16plex_10B_8.raw	Raw
	12Sept2023_CE_Exp4_16plex_10C_2.raw	Raw
	12Sept2023_CE_Exp4_16plex_20C_3.raw	Raw

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Publications

The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel K<sub>V</sub>11.1 associated with long QT syndrome.

Egly Christian L CL Barny Lea A LA Do Tri T McDonald Eli F EF Knollmann Björn C BC Plate Lars L

The Journal of biological chemistry 20240612 7

The voltage-gated potassium ion channel K<sub>V</sub>11.1 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 facto ...[more]

PMID: 38876300

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