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Functional consequences of the interactions among the neural cell adhesion molecule NCAM, the receptor tyrosine kinase TrkB, and the inwardly rectifying K+ channel KIR3.3.
Kleene R
,
Cassens C
,
Bähring R
,
Theis T
,
Xiao MF
,
Dityatev A
,
Schafer-Nielsen C
,
Döring F
,
Wischmeyer E
,
Schachner M
.
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Cell adhesion molecules and neurotrophin receptors are crucial for the development and the function of the nervous system. Among downstream effectors of neurotrophin receptors and recognition molecules are ion channels. Here, we provide evidence that G protein-coupled inwardly rectifying K(+) channel Kir3.3 directly binds to the neural cell adhesion molecule (NCAM) and neurotrophin receptor TrkB. We identified the binding sites for NCAM and TrkB at the C-terminal intracellular domain of Kir3.3. The interaction between NCAM, TrkB, and Kir3.3 was supported by immunocytochemical co-localization of Kir3.3, NCAM, and/or TrkB at the surface of hippocampal neurons. Co-expression of TrkB and Kir3.1/3.3 in Xenopus oocytes increased the K(+) currents evoked by Kir3.1/3.3 channels. This current enhancement was reduced by the concomitant co-expression with NCAM. Both surface fluorescence measurements of microinjected oocytes and cell surface biotinylation of transfected CHO cells indicated that the cell membrane localization of Kir3.3 is regulated by TrkB and NCAM. Furthermore, the level of Kir3.3, but not of Kir3.2, at the plasma membranes was reduced in TrkB-deficient mice, supporting the notion that TrkB regulates the cell surface expression of Kir3.3. The premature expression of developmentally late appearing Kir3.1/3.3 in hippocampal neurons led to a reduction of NCAM-induced neurite outgrowth. Our observations indicate a decisive role for the neuronal K(+) channel in regulating NCAM-dependent neurite outgrowth and attribute a physiologically meaningful role to the functional interplay of Kir3.3, NCAM, and TrkB in ontogeny.
Barbacid,
The Trk family of neurotrophin receptors.
1994, Pubmed
Barbacid,
The Trk family of neurotrophin receptors.
1994,
Pubmed
Bergami,
Conditional deletion of TrkB alters adult hippocampal neurogenesis and anxiety-related behavior.
2009,
Pubmed
Beuten,
Association of specific haplotypes of neurotrophic tyrosine kinase receptor 2 gene (NTRK2) with vulnerability to nicotine dependence in African-Americans and European-Americans.
2007,
Pubmed
Brennaman,
NCAM in neuropsychiatric and neurodegenerative disorders.
2010,
Pubmed
Cassens,
Binding of the receptor tyrosine kinase TrkB to the neural cell adhesion molecule (NCAM) regulates phosphorylation of NCAM and NCAM-dependent neurite outgrowth.
2010,
Pubmed
Delling,
The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts.
2002,
Pubmed
,
Xenbase
Dityatev,
Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses.
2004,
Pubmed
Dityatev,
Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM.
2000,
Pubmed
Doherty,
A threshold effect of the major isoforms of NCAM on neurite outgrowth.
1990,
Pubmed
Edelman,
Early epochal maps of two different cell adhesion molecules.
1983,
Pubmed
Grosse,
Axonal sorting of Kir3.3 defines a GABA-containing neuron in the CA3 region of rodent hippocampus.
2003,
Pubmed
Ippolito,
N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase activity of Galphai.
2002,
Pubmed
,
Xenbase
Isomoto,
Inwardly rectifying potassium channels: their molecular heterogeneity and function.
1997,
Pubmed
,
Xenbase
Iwasaki,
Sequential cis/trans autophosphorylation in TrkB tyrosine kinase.
1997,
Pubmed
Jelacic,
Functional and biochemical evidence for G-protein-gated inwardly rectifying K+ (GIRK) channels composed of GIRK2 and GIRK3.
2000,
Pubmed
Kaplan,
Neurotrophin signal transduction in the nervous system.
2000,
Pubmed
Karschin,
IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain.
1996,
Pubmed
Klein,
trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development.
1989,
Pubmed
Klein,
The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.
1991,
Pubmed
Koyrakh,
Molecular and cellular diversity of neuronal G-protein-gated potassium channels.
2005,
Pubmed
Kozell,
Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol.
2009,
Pubmed
Kramer,
Absence of Ret signaling in mice causes progressive and late degeneration of the nigrostriatal system.
2007,
Pubmed
Lüthi,
H-current: properties of a neuronal and network pacemaker.
1998,
Pubmed
Martinowich,
New insights into BDNF function in depression and anxiety.
2007,
Pubmed
Maćkowiak,
Acute and repeated administration of cocaine differentially regulates expression of PSA-NCAM-positive neurons in the rat hippocampus.
2005,
Pubmed
Middlemas,
trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors.
1991,
Pubmed
Murase,
The role of cell adhesion molecules in synaptic plasticity and memory.
1999,
Pubmed
Rogalski,
TrkB activation by brain-derived neurotrophic factor inhibits the G protein-gated inward rectifier Kir3 by tyrosine phosphorylation of the channel.
2000,
Pubmed
,
Xenbase
Schachner,
Neural recognition molecules and synaptic plasticity.
1997,
Pubmed
Soppet,
The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor.
1991,
Pubmed
Squinto,
trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor.
1991,
Pubmed
Stork,
Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM).
1997,
Pubmed
Stork,
Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice.
1999,
Pubmed
Tannahill,
The neurotrophin receptors TrkA and TrkB are inhibitory for neurite outgrowth.
1995,
Pubmed
Torrecilla,
G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons.
2002,
Pubmed
Wischmeyer,
Subunit interactions in the assembly of neuronal Kir3.0 inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase
Xu,
Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence.
2007,
Pubmed
