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The four and a half LIM domain protein 2 interacts with and regulates the HERG channel
Author(s) -
Lin Jijin,
Lin Shuguang,
Yu Xiyong,
Choy Patrick C.,
Shen Xiuzhang,
Deng Chunyu,
Kuang Sujuan,
Wu Jun
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06596.x
Subject(s) - herg , microbiology and biotechnology , potassium channel , immunoprecipitation , ion channel , protein subunit , hek 293 cells , chemistry , patch clamp , biology , biochemistry , biophysics , gene , receptor
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 α‐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.