KChAP as a chaperone for specific K(+) channels.
The concept of chaperones for K(+) channels is new. Recently, we discovered a novel molecular chaperone, KChAP, which increased total Kv2.1 protein and functional channels in Xenopus oocytes through a transient interaction with the Kv2.1 amino terminus. Here we report that KChAP is a chaperone for Kv1.3 and Kv4.3. KChAP increased the amplitude of Kv1.3 and Kv4.3 currents without affecting kinetics or voltage dependence, but had no such effect on Kv1.1, 1.2, 1.4, 1.5, 1.6, and 3.1 or Kir2.2, HERG, or KvLQT1. Although KChAP belongs to a family of proteins that interact with transcription factors, upregulation of channel currents was not blocked by the transcription inhibitor actinomycin D. A 98-amino acid fragment of KChAP binds to the channel and is indistinguishable from KChAP in its enhancement of Kv4.3 current and protein levels. Using a KChAP antibody, we have coimmunoprecipitated KChAP with Kv2.1 and Kv4.3 from heart. We propose that KChAP is a chaperone for specific Kv channels and may have this function in cardiomyocytes where Kv4.3 produces the transient outward current, I(to).
Kuryshev
Y A
YA
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
Gudz
T I
TI
Brown
A M
AM
Wible
B A
BA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel; D007739:L Cells; D051379:Mice; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D050828:Protein Inhibitors of Activated STAT; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels; D014158:Transcription, Genetic; D014981:Xenopus
D051668:Delayed Rectifier Potassium Channels; C496974:Kcna3 protein, mouse; C496975:Kcna3 protein, rat; C496990:Kcnb1 protein, mouse; C496991:Kcnb1 protein, rat; C497022:Kcnd3 protein, mouse; C497023:Kcnd3 protein, rat; D051664:Kv1.3 Potassium Channel; D018832:Molecular Chaperones; C112253:Pias3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels