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J Neurosci
2004 Nov 24;2447:10750-62. doi: 10.1523/JNEUROSCI.3300-04.2004.
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Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction.
Santoro B
,
Wainger BJ
,
Siegelbaum SA
.
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Hyperpolarization-activated cation currents (I(h)) are carried by channels encoded by a family of four genes (HCN1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. HCN1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density of I(h). Expression of I(h) is also regulated by neuronal activity. To isolate proteins that may control HCN channel expression or function, we performed yeast two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as bait. We identified a brain-specific protein, which has been previously termed TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p-related protein), that specifically interacts with all four HCN channels through a conserved sequence in their C-terminal tails. In situ hybridization and immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is disrupted after deletion of HCN1 through homologous recombination, demonstrating a key in vivo interaction between HCN1 and TRIP8b. TRIP8b dramatically alters the trafficking of HCN channels heterologously expressed in Xenopus oocytes and human embryonic kidney 293 cells, causing a specific decrease in surface expression of HCN protein and I(h) density, with a pronounced intracellular accumulation of HCN protein that is colocalized in discrete cytoplasmic clusters with TRIP8b. Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases native I(h) density. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane.
Amery,
Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals.
2001, Pubmed
Amery,
Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals.
2001,
Pubmed
Arikkath,
Auxiliary subunits: essential components of the voltage-gated calcium channel complex.
2003,
Pubmed
Bender,
Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus.
2001,
Pubmed
Berger,
High I(h) channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs.
2001,
Pubmed
Blatch,
The tetratricopeptide repeat: a structural motif mediating protein-protein interactions.
1999,
Pubmed
Brewster,
Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner.
2002,
Pubmed
Brãuer,
Molecular and functional analysis of hyperpolarization-activated pacemaker channels in the hippocampus after entorhinal cortex lesion.
2001,
Pubmed
Chaplan,
Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain.
2003,
Pubmed
Chen,
Functional roles of charged residues in the putative voltage sensor of the HCN2 pacemaker channel.
2000,
Pubmed
,
Xenbase
Chen,
Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability.
2001,
Pubmed
Chen,
Rab8b and its interacting partner TRIP8b are involved in regulated secretion in AtT20 cells.
2001,
Pubmed
Drake,
Ultrastructural localization of full-length trkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity.
1999,
Pubmed
Evans,
Electrophysiology of embryonic, adult and aged rat hippocampal neurons in serum-free culture.
1998,
Pubmed
Gatto,
Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5.
2000,
Pubmed
Huber,
Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p.
1993,
Pubmed
Kass,
Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmias.
2003,
Pubmed
Kowdley,
Hyperpolarization-activated chloride currents in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Lörincz,
Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites.
2002,
Pubmed
MacLean,
Activity-independent homeostasis in rhythmically active neurons.
2003,
Pubmed
,
Xenbase
Magee,
Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons.
1998,
Pubmed
Moosmang,
Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues.
2001,
Pubmed
Nolan,
The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells.
2003,
Pubmed
Nolan,
A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons.
2004,
Pubmed
Notomi,
Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain.
2004,
Pubmed
O'Dell,
Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger.
1991,
Pubmed
Peränen,
Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts.
1996,
Pubmed
Qu,
MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes.
2004,
Pubmed
Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed
Santoro,
Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS.
2000,
Pubmed
,
Xenbase
Santoro,
The multiple personalities of h-channels.
2003,
Pubmed
Santoro,
Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels.
1997,
Pubmed
Santoro,
Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain.
1998,
Pubmed
,
Xenbase
Santoro,
Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction.
2004,
Pubmed
,
Xenbase
Sheng,
Molecular organization of the postsynaptic specialization.
2001,
Pubmed
Vasilyev,
Postnatal development of the hyperpolarization-activated excitatory current Ih in mouse hippocampal pyramidal neurons.
2002,
Pubmed
Wainger,
Molecular mechanism of cAMP modulation of HCN pacemaker channels.
2001,
Pubmed
Wang,
Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications.
2003,
Pubmed
Xue,
Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: insights into structure-function relationships and multimerization.
2002,
Pubmed
,
Xenbase
Yan,
Immunocytochemical localization of TrkB in the central nervous system of the adult rat.
1997,
Pubmed
Yu,
MinK-related peptide 1: A beta subunit for the HCN ion channel subunit family enhances expression and speeds activation.
2001,
Pubmed
,
Xenbase
Zerial,
Rab proteins as membrane organizers.
2001,
Pubmed
van Welie,
Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated Ih channels.
2004,
Pubmed
