The C‐terminus of Kv7 channels: a multifunctional module
- 31 March 2008
- journal article
- review article
- Published by Wiley in The Journal of Physiology
- Vol. 586 (7), 1803-1810
- https://doi.org/10.1113/jphysiol.2007.149187
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 alpha 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.This publication has 58 references indexed in Scilit:
- Calmodulin regulates the trafficking of KCNQ2 potassium channelsThe FASEB Journal, 2007
- Activation of Epidermal Growth Factor Receptor Inhibits KCNQ2/3 Current through Two Distinct Pathways: Membrane PtdIns(4,5)P2Hydrolysis and Channel PhosphorylationJournal of Neuroscience, 2007
- Structural Insight into KCNQ (Kv7) Channel Assembly and ChannelopathyNeuron, 2007
- Integration of Phosphoinositide- and Calmodulin-Mediated Regulation of TRPC6Molecular Cell, 2007
- Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domainsProceedings of the National Academy of Sciences of the United States of America, 2006
- Structural Determinants of M-Type KCNQ (Kv7) K+Channel AssemblyJournal of Neuroscience, 2006
- Novel mutations in the KCNQ2 gene link epilepsy to a dysfunction of the KCNQ2-calmodulin interactionJournal of Medical Genetics, 2004
- AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonistsNature Neuroscience, 2003
- Rapid ReportThe Journal of Physiology, 2003
- Calcium-Binding Proteins: Intracellular Sensors from the Calmodulin SuperfamilyBiochemical and Biophysical Research Communications, 2002