Angiotensin receptor type 1 forms a complex with the transient outward potassium channel Kv4.3 and regulates its gating properties and intracellular localization.
We report a novel signal transduction complex of the angiotensin receptor type 1. In this complex the angiotensin receptor type 1 associates with the potassium channel alpha-subunit Kv4.3 and regulates its intracellular distribution and gating properties. Co-localization of Kv4.3 with angiotensin receptor type 1 and fluorescent resonance energy transfer between those two proteins labeled with cyan and yellow-green variants of green fluorescent protein revealed that Kv4.3 and angiotensin receptor type I are located in close proximity to each other in the cell. The angiotensin receptor type 1 also co-immunoprecipitates with Kv4.3 from canine ventricle or when co-expressed with Kv4.3 and its beta-subunit KChIP2 in human embryonic kidney 293 cells. Treatment of the cells with angiotensin II results in the internalization of Kv4.3 in a complex with the angiotensin receptor type 1. When stimulated with angiotensin II, angiotensin receptors type 1 modulate gating properties of the remaining Kv4.3 channels on the cell surface by shifting their activation voltage threshold to more positive values. We hypothesize that the angiotensin receptor type 1 provides its internalization molecular scaffold to Kv4.3 and in this way regulates the cell surface representation of the ion channel.
Doronin
Sergey V
SV
Department of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. sdoronin@notes.cc.sunysb.edu
Potapova
Irina A
IA
Lu
Zhongju
Z
Cohen
Ira S
IS
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D046911:Macromolecular Substances; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels; D015398:Signal Transduction / Q000502:physiology*; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism
D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; C497021:KCND3 protein, human; C496752:KCNIP2 protein, human; C497023:Kcnd3 protein, rat; C496758:Kcnip2 protein, rat; D051605:Kv Channel-Interacting Proteins; D046911:Macromolecular Substances; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D044140:Receptor, Angiotensin, Type 1; D011993:Recombinant Fusion Proteins; D051672:Shal Potassium Channels; D000804:Angiotensin II