title: KChIP-like auxiliary subunits of Kv4 channels regulate excitability of muscle cells and control male turning behavior during mating in Caenorhabditis elegans.
abstract: 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. Here, we identified three C. elegans KChIP-like (ceKChIP) proteins, NCS-4, NCS-5, and NCS-7. All three ceKChIPs alter electrical characteristics of SHL-1, a C. elegans Kv4 channel ortholog, currents by slowing down inactivation kinetics and shifting voltage dependence of activation to more hyperpolarizing potentials. Native SHL-1 current is completely abolished in cultured myocytes of Triple KO worms in which all three ceKChIP genes are deleted. Reexpression of NCS-4 partially restored expression of functional SHL-1 channels, whereas NCS-4(efm), a NCS-4 mutant with impaired Ca(2+)-binding ability, only enhanced expression of SHL-1 proteins, but failed to transport them from the Golgi apparatus to the cell membrane in body wall muscles of Triple KO worms. Moreover, translational reporter revealed that NCS-4 assembles with SHL-1 K(+) channels in male diagonal muscles. Deletion of either ncs-4 or shl-1 significantly impairs male turning, a behavior controlled by diagonal muscles during mating. The phenotype of the ncs-4 null mutant could be rescued by reexpression of NCS-4, but not NCS-4(efm), further emphasizing the importance of Ca(2+) binding to ceKChIPs in regulating native SHL-1 channel function. Together, these data reveal an evolutionarily conserved mechanism underlying the regulation of Kv4 channels by KChIPs and unravel critical roles of ceKChIPs in regulating muscle cell excitability and animal behavior in C. elegans.
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and University of Chinese Academy of Sciences, Shanghai 200031, P. R. China.
authors: Xin
authors: X
authors: Chen
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and.
authors: Mei-Yu
authors: MY
authors: Ruan
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and sqcai@ion.ac.cn.
authors: Shi-Qing
authors: SQ
authors: Cai
mesh_terms: D000200:Action Potentials; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012726:Sexual Behavior, Animal; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051605:Kv Channel-Interacting Proteins; C000596798:NCS-4 protein, C elegans; C000596799:NCS-5 protein, C elegans; C000596800:NCS-7 protein, C elegans; D051580:Neuronal Calcium-Sensor Proteins; D051672:Shal Potassium Channels; D002118:Calcium
keywords: C. elegans; KChIP; calcium binding; male mating; potassium channel; turing behavior
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