The C-terminus of Kv7 channels: a multifunctional module

Authors


  • This report was presented at a symposium on Kv7 (KCNQ) potassium channels that are mutated in human diseases, held at a joint meeting of The Slovak Physiological Society, The Physiological Society and The Federation of European Physiological Societies in Bratislava, Slovakia on 14 September 2007. It was commissioned by the Editorial Board and reflects the views of the authors.

Corresponding author B. Attali: Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Tel Aviv 69978, Israel.  Email: battali@post.tau.ac.il

Abstract

Kv7 channels (KCNQ) represent a family of voltage-gated K+ channels which plays a prominent role in brain and cardiac excitability. Their physiological importance is underscored by the existence of mutations in human Kv7 genes, leading to severe cardiovascular and neurological disorders such as the cardiac long QT syndrome and neonatal epilepsy. Kv7 channels exhibit some structural and functional features that are distinct from other Kv channels. Notably, the Kv7 C-terminus is long compared to other K+ channels and is endowed with characteristic structural domains, including coiled-coils, amphipatic α helices containing calmodulin-binding motifs and basic amino acid clusters. Here we provide a brief overview of current insights and as yet unsettled issues about the structural and functional attributes of the C-terminus of Kv7 channels. Recent data indicate that the proximal half of the Kv7 C-terminus associates with one calmodulin constitutively bound to each subunit. Epilepsy and long QT mutations located in this proximal region impair calmodulin binding and can affect channel gating, folding and trafficking. The distal half of the Kv7 C-terminus directs tetramerization, employing tandem coiled-coils. Together, the data indicate that the Kv7 C-terminal domain is a multimodular structure playing a crucial role in channel gating, assembly and trafficking as well as in scaffolding the channel complex with signalling proteins.

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