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J Neurosci
2002 Aug 15;2216:7154-64. doi: 20026702.
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The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts.
Delling M, Wischmeyer E, Dityatev A, Sytnyk V, Veh RW, Karschin A, Schachner M.
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Mice deficient in the neural cell adhesion molecule (NCAM) exhibit increased anxiety and anxiolytic sensitivity to serotonin 5-HT1A receptor agonists. Here, we investigate the relationship between NCAM and 5-HT1A receptor signaling pathways modulating G-protein-activated inwardly rectifying K+ (Kir3) channels. When studying this relationship in cultured hippocampal neurons, we observed that in cells from NCAM-deficient mice, inwardly rectifying K+ (Kir3) currents were increased compared with wild-type controls. Analysis of this modulatory mechanism in Xenopus oocytes and Chinese hamster ovary (CHO) cells revealed that the recombinantly expressed major transmembrane isoforms NCAM140 and NCAM180 specifically reduced inward currents generated by neuronal Kir3.1/3.2 and Kir3.1/3.3 but not by cardiac Kir3.1/3.4 channels. Using fluorescence measurements and surface biotinylation assays, we show that this effect was caused by a reduced surface localization of Kir3 channels. Furthermore, expression of flag-tagged Kir3 channels in cultured neurons of NCAM-deficient mice resulted in a higher transport of these channels into neurites and a higher cell-surface localization compared with wild-type neurons. Neuronal Kir3 channels and NCAM isoforms are associated with cholesterol-rich microdomains (lipid rafts) in CHO cells and in isolated brain membranes. Mutational and pharmacological disruption of the lipid raft association of NCAM140 normalizes surface delivery of channels. We conclude that the transmembrane isoforms of NCAM reduce the transport of Kir3 channels to the cell surface via lipid rafts. Thus, regulation of Kir3 channel activity by NCAM may represent a novel mechanism controlling long-term excitability of neurons.
Beggs,
NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn).
1997, Pubmed
Beggs,
NCAM140 interacts with the focal adhesion kinase p125(fak) and the SRC-related tyrosine kinase p59(fyn).
1997,
Pubmed Brown,
Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth.
1980,
Pubmed Cremer,
Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning.
1994,
Pubmed Dityatev,
Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM.
2000,
Pubmed Drake,
GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus.
1997,
Pubmed Ethell,
Cell surface heparan sulfate proteoglycan syndecan-2 induces the maturation of dendritic spines in rat hippocampal neurons.
1999,
Pubmed Fenton,
Regulation of intracellular actin polymerization by prenylated cellular proteins.
1992,
Pubmed Hansen,
Cholesterol depletion of enterocytes. Effect on the Golgi complex and apical membrane trafficking.
2000,
Pubmed Hess,
Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide.
1993,
Pubmed Hooper,
Glycosyl-phosphatidylinositol anchored membrane enzymes.
1997,
Pubmed Inanobe,
Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra.
1999,
Pubmed
,
Xenbase Jelacic,
Functional and biochemical evidence for G-protein-gated inwardly rectifying K+ (GIRK) channels composed of GIRK2 and GIRK3.
2000,
Pubmed Keller,
Cholesterol is required for surface transport of influenza virus hemagglutinin.
1998,
Pubmed Kennedy,
GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels.
1999,
Pubmed Kolkova,
Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway.
2000,
Pubmed Little,
Palmitoylation of the cytoplasmic domain of the neural cell adhesion molecule N-CAM serves as an anchor to cellular membranes.
1998,
Pubmed Lüscher,
G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons.
1997,
Pubmed Ma,
Role of ER export signals in controlling surface potassium channel numbers.
2001,
Pubmed
,
Xenbase Martens,
Differential targeting of Shaker-like potassium channels to lipid rafts.
2000,
Pubmed Martens,
Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae.
2001,
Pubmed Melkonian,
Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated.
1999,
Pubmed Mohammadi,
Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.
1998,
Pubmed Montixi,
Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains.
1998,
Pubmed Morishige,
Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells.
1999,
Pubmed Murase,
The role of cell adhesion molecules in synaptic plasticity and memory.
1999,
Pubmed Niethammer,
Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis.
2002,
Pubmed Patterson,
Novel inhibitory action of tunicamycin homologues suggests a role for dynamic protein fatty acylation in growth cone-mediated neurite extension.
1994,
Pubmed Pierini,
Flotillas of lipid rafts fore and aft.
2001,
Pubmed Resh,
Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins.
1999,
Pubmed Retzer,
Production and characterization of chimeric transferrins for the determination of the binding domains for bacterial transferrin receptors.
1996,
Pubmed Rønn,
The neural cell adhesion molecule (NCAM) in development and plasticity of the nervous system.
1998,
Pubmed Schachner,
Neural recognition molecules and synaptic plasticity.
1997,
Pubmed Schmidt,
Synaptic-like microvesicles of neuroendocrine cells originate from a novel compartment that is continuous with the plasma membrane and devoid of transferrin receptor.
1997,
Pubmed Schuster,
Increase in proportion of hippocampal spine synapses expressing neural cell adhesion molecule NCAM180 following long-term potentiation.
1998,
Pubmed Simon,
Molecular Association of the Neural Adhesion Molecules L1 and N-CAM in the Surface Membrane of Neuroblastoma Cells is Shown by Chemical Cross-linking.
1991,
Pubmed Simons,
Functional rafts in cell membranes.
1997,
Pubmed Sontheimer,
The Neural Cell Adhesion Molecule (N-CAM) Modulates K+ Channels in Cultured Glial Precursor Cells.
1991,
Pubmed Stevens,
Identification of regions that regulate the expression and activity of G protein-gated inward rectifier K+ channels in Xenopus oocytes.
1997,
Pubmed
,
Xenbase 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 Stork,
Recovery of emotional behaviour in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180.
2000,
Pubmed Wischmeyer,
Subunit interactions in the assembly of neuronal Kir3.0 inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase Zhao,
Identification of a homophilic binding site in immunoglobulin-like domain 2 of the cell adhesion molecule L1.
1998,
Pubmed
