title: Screening for cardiac HERG potassium channel interacting proteins using the yeast two-hybrid technique.
abstract: The human ERG protein (HERG or Kv 11.1) encoded by the human ether-a-go-go-related gene (herg) is the pore-forming subunit of the cardiac delayed rectifier potassium current (IKr) responsible for action potential (AP) repolarization. Mutations in HERG lead to long-QT syndrome, a major cause of arrhythmias. Protein-protein interactions are fundamental for ion channel trafficking, membrane localization, and functional modulation. To identify proteins involved in the regulation of the HERG channel, we conducted a yeast two-hybrid screen of a human heart cDNA library using the C-terminus or N-terminus of HERG as bait. Fifteen proteins were identified as HERG amino terminal (HERG-NT)-interacting proteins, including Caveolin-1 (a membrane scaffold protein with multiple interacting partners, including G-proteins, kinases and NOS), the zinc finger protein, FHL2 and PTPN12 (a non-receptor tyrosine phosphatase). Eight HERG carboxylic terminal (HERG-CT)-interacting proteins were also identified, including the NF-κB-interacting protein myotrophin, We have identified multiple potential interacting proteins that may regulate cardiac IKr through cytoskeletal interactions, G-protein modulation, phosphorylation and downstream second messenger and transcription cascades. These findings provide further insight into dynamic modulation of HERG under physiological conditions and arrhythmogenesis.
authors.affiliation: Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Ma
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Jijin
authors.initials: J
authors.lastname: Lin
authors.forename: Yifan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Shen
authors.forename: Li
authors.initials: L
authors.lastname: Ren
mesh_terms: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps; D020798:Two-Hybrid System Techniques
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human
keywords: Potassium channel; Protein-protein interaction; Yeast two-hybrid; herg (Human ether-a-go-go related gene)