Auto-phosphorylation of a voltage-gated K+ channel controls non-associative learning.
Here, we characterize a new K(+) channel-kinase complex that operates in the metazoan Caenorhabditis elegans to control learning behaviour. This channel is composed of a pore-forming subunit, dubbed KHT-1 (73% homology to human Kv3.1), and the accessory subunit MPS-1, which shows kinase activity. Genetic, biochemical and electrophysiological evidence show that KHT-1 and MPS-1 form a complex in vitro and in native mechanosensory PLM neurons, and that KHT-1 is a substrate for the kinase activity of MPS-1. Behavioural analysis further shows that the kinase activity of MPS-1 is specifically required for habituation to repetitive mechanical stimulation. Thus, worms bearing an inactive MPS-1 variant (D178N) respond normally to touch on the body but do not habituate to repetitive mechanical stimulation such as tapping on the side of the Petri dish. Hence, the phosphorylation status of KHT-1-MPS-1 seems to be linked to distinct behavioural responses. In the non-phosphorylated state the channel is necessary for the normal function of the touch neurons. In the auto-phosphorylated state the channel acts to induce neuronal adaptation to mechanical stimulation. Taken together, these data establish a new mechanism of dynamic regulation of electrical signalling in the nervous system.
Cai
Shi-Qing
SQ
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA.
Wang
Yi
Y
Park
Ki Ho
KH
Tong
Xin
X
Pan
Zui
Z
Sesti
Federico
F
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009474:Neurons / Q000737:chemistry; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; C473893:MPS-1 protein, C elegans; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated