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The C‐terminus of Kv7 channels: a multifunctional module
Author(s) -
Haitin Yoni,
Attali Bernard
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.149187
Subject(s) - gating , calmodulin , c terminus , microbiology and biotechnology , long qt syndrome , protein subunit , neuroscience , ion channel , biology , chemistry , gene , biochemistry , amino acid , medicine , receptor , qt interval , enzyme
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.