The four and a half LIM domain protein 2 interacts with and regulates the HERG channel.
Protein-protein interactions are critical for protein trafficking, localization and the regulation of ion channels. The human ether-a-go-go-related gene (herg) encodes the alpha-subunit of the potassium channel underlying the rapid component of the cardiac delayed rectifier current. To identify the cellular proteins involved in the regulation of the HERG channel, a human heart cDNA library was screened using a yeast two-hybrid system, with the N-terminus of HERG as bait. The four and a half LIM domain protein 2 (FHL2) was identified as a potential HERG partner. The interaction between these two proteins was confirmed by co-immunoprecipitation and glutathione transferase pull-down assays and immunocytochemical analysis. The physiological implication of HERG-FHL2 interaction, assessed by whole-cell, patch-clamp electrophysiology experiments, showed a significant increase in the HERG current amplitude and a faster deactivation of the tail current in human embryonic kidney 293 cells co-expressing HERG and FHL2. These data indicate that FHL2 interacts with and regulates the HERG channel. Our findings may aid in the further understanding of the molecular basis of HERG channel diversity and arrhythmogenesis in the long-QT syndrome.
Lin
Jijin
J
Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, China.
Lin
Shuguang
S
Yu
Xiyong
X
Choy
Patrick C
PC
Shen
Xiuzhang
X
Deng
Chunyu
C
Kuang
Sujuan
S
Wu
Jun
J
D000818:Animals; D002460:Cell Line; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels / Q000032:analysis / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; C000606913:KCNH2 protein, human; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors