DNA topoisomerase 2-associated proteins PATL1 and PATL2 regulate the biogenesis of hERG K channels.

The human ether-a-go-go-related gene (hERG) K channel conducts a rapidly activating delayed rectifier K current (I), which is essential for normal electrical activity of the heart. Precise regulation of hERG channel biogenesis is critical for serving its physiological functions, and deviations from the regulation result in human diseases. However, the mechanism underlying the precise regulation of hERG channel biogenesis remains elusive.

Tetrameric Assembly of K Channels Requires ER-Located Chaperone Proteins.

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.

KChIP-like auxiliary subunits of Kv4 channels regulate excitability of muscle cells and control male turning behavior during mating in Caenorhabditis elegans.

Voltage-gated Kv4 channels control the excitability of neurons and cardiac myocytes by conducting rapidly activating-inactivating currents. The function of Kv4 channels is profoundly modulated by K(+) channel interacting protein (KChIP) soluble auxiliary subunits. However, the in vivo mechanism of the modulation is not fully understood.