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.
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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, Ralf; Cassens, Claas; Bähring, Robert; Theis, Thomas; Xiao, Meifang; Dityatev, Alexander; Schafer-Nielsen, Claus; Döring, Frank; Wischmeyer, Erhard; Schachner, Melitta.
in: J BIOL CHEM, Jahrgang 285, Nr. 37, 37, 2010, S. 28968-28979.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - 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.
AU - Kleene, Ralf
AU - Cassens, Claas
AU - Bähring, Robert
AU - Theis, Thomas
AU - Xiao, Meifang
AU - Dityatev, Alexander
AU - Schafer-Nielsen, Claus
AU - Döring, Frank
AU - Wischmeyer, Erhard
AU - Schachner, Melitta
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 285
SP - 28968
EP - 28979
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 37
M1 - 37
ER -