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Biophys J
2015 Jun 02;10811:2658-69. doi: 10.1016/j.bpj.2015.04.024.
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Different KChIPs compete for heteromultimeric assembly with pore-forming Kv4 subunits.
Zhou J, Tang Y, Zheng Q, Li M, Yuan T, Chen L, Huang Z, Wang K.
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Auxiliary Kv channel-interacting proteins 1-4 (KChIPs1-4) coassemble with pore-forming Kv4 α-subunits to form channel complexes underlying somatodendritic subthreshold A-type current that regulates neuronal excitability. It has been hypothesized that different KChIPs can competitively bind to Kv4 α-subunit to form variable channel complexes that can exhibit distinct biophysical properties for modulation of neural function. In this study, we use single-molecule subunit counting by total internal reflection fluorescence microscopy in combinations with electrophysiology and biochemistry to investigate whether different isoforms of auxiliary KChIPs, KChIP4a, and KChIP4bl, can compete for binding of Kv4.3 to coassemble heteromultimeric channel complexes for modulation of channel function. To count the number of photobleaching steps solely from cell membrane, we take advantage of a membrane tethered k-ras-CAAX peptide that anchors cytosolic KChIP4 proteins to the surface for reduction of background noise. Single-molecule subunit counting reveals that the number of KChIP4 isoforms in Kv4.3-KChIP4 complexes can vary depending on the KChIP4 expression level. Increasing the amount of KChIP4bl gradually reduces bleaching steps of KChIP4a isoform proteins, and vice versa. Further analysis of channel gating kinetics from different Kv4-KChIP4 subunit compositions confirms that both KChIP4a and KChIP4bl can modulate the channel complex function upon coassembly. Taken together, our findings show that auxiliary KChIPs can heteroassemble with Kv4 in a competitive manner to form heteromultimeric Kv4-KChIP4 channel complexes that are biophysically distinct and regulated under physiological or pathological conditions.
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000, Pubmed,
Xenbase
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000,
Pubmed
,
Xenbase Baranauskas,
Cell-type-specific splicing of KChIP4 mRNA correlates with slower kinetics of A-type current.
2004,
Pubmed
,
Xenbase Bernard,
Acquired dendritic channelopathy in temporal lobe epilepsy.
2004,
Pubmed Burgoyne,
Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling.
2007,
Pubmed Cai,
Unique roles of SK and Kv4.2 potassium channels in dendritic integration.
2004,
Pubmed Chen,
Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.
2006,
Pubmed Choy,
Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi.
1999,
Pubmed Covarrubias,
The neuronal Kv4 channel complex.
2008,
Pubmed Cui,
Enhanced trafficking of tetrameric Kv4.3 channels by KChIP1 clamping.
2008,
Pubmed
,
Xenbase Decher,
Novel KChIP2 isoforms increase functional diversity of transient outward potassium currents.
2004,
Pubmed
,
Xenbase Hancock,
Ras proteins: different signals from different locations.
2003,
Pubmed Hastie,
AMPA receptor/TARP stoichiometry visualized by single-molecule subunit counting.
2013,
Pubmed
,
Xenbase Hoffman,
K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
1997,
Pubmed Holmqvist,
Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.
2002,
Pubmed
,
Xenbase Holmqvist,
Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins.
2001,
Pubmed
,
Xenbase Hu,
The kv4.2 potassium channel subunit is required for pain plasticity.
2006,
Pubmed Jerng,
Multiple Kv channel-interacting proteins contain an N-terminal transmembrane domain that regulates Kv4 channel trafficking and gating.
2008,
Pubmed Jerng,
Molecular physiology and modulation of somatodendritic A-type potassium channels.
2004,
Pubmed Jerng,
Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties.
2005,
Pubmed
,
Xenbase Jeyaraj,
Circadian rhythms govern cardiac repolarization and arrhythmogenesis.
2012,
Pubmed Ji,
Functional stoichiometry of the unitary calcium-release-activated calcium channel.
2008,
Pubmed Kim,
Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons.
2007,
Pubmed Kitazawa,
The stoichiometry and biophysical properties of the Kv4 potassium channel complex with K+ channel-interacting protein (KChIP) subunits are variable, depending on the relative expression level.
2014,
Pubmed
,
Xenbase Kuo,
A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.
2001,
Pubmed Liang,
Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
2009,
Pubmed
,
Xenbase Liang,
Functional rescue of Kv4.3 channel tetramerization mutants by KChIP4a.
2010,
Pubmed
,
Xenbase Liss,
Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription.
2001,
Pubmed Maffie,
Weighing the evidence for a ternary protein complex mediating A-type K+ currents in neurons.
2008,
Pubmed Massone,
RNA polymerase III drives alternative splicing of the potassium channel-interacting protein contributing to brain complexity and neurodegeneration.
2011,
Pubmed Morohashi,
Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4.
2002,
Pubmed Nadal,
The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels.
2003,
Pubmed
,
Xenbase Nakajo,
Stoichiometry of the KCNQ1 - KCNE1 ion channel complex.
2010,
Pubmed
,
Xenbase Norris,
Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in the generation of Kv4-encoded IA channels in cortical pyramidal neurons.
2010,
Pubmed O'Callaghan,
Residues within the myristoylation motif determine intracellular targeting of the neuronal Ca2+ sensor protein KChIP1 to post-ER transport vesicles and traffic of Kv4 K+ channels.
2003,
Pubmed Panama,
Nuclear factor kappaB downregulates the transient outward potassium current I(to,f) through control of KChIP2 expression.
2011,
Pubmed Pioletti,
Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer.
2006,
Pubmed
,
Xenbase Plant,
Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits.
2014,
Pubmed Rhodes,
KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.
2004,
Pubmed Scannevin,
Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1.
2004,
Pubmed Schwenk,
NMR analysis of KChIP4a reveals structural basis for control of surface expression of Kv4 channel complexes.
2008,
Pubmed Takimoto,
Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels.
2002,
Pubmed Tang,
Auxiliary KChIP4a suppresses A-type K+ current through endoplasmic reticulum (ER) retention and promoting closed-state inactivation of Kv4 channels.
2013,
Pubmed Ulbrich,
Rules of engagement for NMDA receptor subunits.
2008,
Pubmed
,
Xenbase Ulbrich,
Subunit counting in membrane-bound proteins.
2007,
Pubmed
,
Xenbase Van Hoorick,
The aromatic cluster in KCHIP1b affects Kv4 inactivation gating.
2007,
Pubmed Wang,
Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.
2007,
Pubmed
,
Xenbase
