Voltage-gated Kv4 channels conduct fast transient K⁺ currents and hence control the excitability of neurons and cardiac myocytes. The properties of Kv4 channels are usually regulated by K⁺ channel interacting proteins (KChIPs), their soluble auxiliary subunits. However, the molecular mechanism underlying the regulation of Kv4 by KChIPs is not fully understood.

　　A study from Dr. CAI Shiqing's lab at the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, identified three C. elegans KChIP-like (ceKChIP) proteins, NCS-4, NCS-5, and NCS-7. Deletion of these three ceKChIP genes completely abolished native SHL-1 (a C. elegans Kv4 channel ortholog) currents in muscle cells of C. elegans, suggesting ceKChIPs are essential for the biogenesis of SHL-1 K⁺ channel. KChIPs belong to the neuronal Ca²⁺ sensor superfamily and each KChIP possesses four Ca²⁺-binding EF hand motifs. The authors also revealed that Ca²⁺ binding to NCS-4 is dispensable for the biogenesis of SHL-1 channels, but essential for transporting SHL-1 proteins from the Golgi apparatus to the cell membrane. These results clarify the role of Ca²⁺ signaling in the modulation of Kv4 by KChIPs.

　　This study also found that NCS-4 assembles with SHL-1 K⁺ channels in male diagonal muscles that control turning behavior during male mating. Deletion of either ncs-4 or shl-1 significantly reduces mating ability, due to over-excitability observed in diagonal muscles of male worms. These results thus unravel critical roles of KChIPs in regulating cell excitability and animal behavior.

　　This research entitled "KChIP-Like Auxiliary Subunits of Kv4 Channels Regulate Excitability of Muscle Cells and Control Male Turning Behavior during Mating in Caenorhabditis elegans" was published in the Journal of Neuroscience on February 4, 2015. This work was mainly carried out by graduate student CHEN Xin and research assistant RUAN Meiyu under the supervision of Dr. CAI Shiqing. It was supported by grants from the National Natural Science Foundation of China .