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The Journal of Neuroscience, December 17, 2008, 28(51):13845-13855; doi:10.1523/JNEUROSCI.3213-08.2008

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Cellular/Molecular
Stable Membrane Expression of Postsynaptic Ca_V1.2 Calcium Channel Clusters Is Independent of Interactions with AKAP79/150 and PDZ Proteins

Valentina Di Biase,¹ Gerald J. Obermair,¹ Zsolt Szabo,¹ Christophe Altier,² Juan Sanguesa,² Emmanuel Bourinet,² and Bernhard E. Flucher¹

¹Department of Physiology and Medical Physics, Innsbruck Medical University, A-6020 Innsbruck, Austria, and ²Département de Physiologie, Laboratoire de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, 34094 Montpellier, France

Correspondence should be addressed to Dr. Bernhard E. Flucher, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria. Email: bernhard.e.flucher{at}i-med.ac.at

In neurons L-type calcium currents contribute to synaptic plasticity and to activity-dependent gene regulation. The subcellular localization of Ca_V1.2 and its association with upstream and downstream signaling proteins is important for efficient and specific signal transduction. Here we tested the hypothesis that A-kinase anchoring proteins (AKAPs) or PDZ-proteins are responsible for the targeting and anchoring of Ca_V1.2 in the postsynaptic compartment of glutamatergic neurons. Double-immunofluorescence labeling of hippocampal neurons transfected with external HA epitope-tagged Ca_V1.2 demonstrated that clusters of membrane-incorporated Ca_V1.2-HA were colocalized with AKAP79/150 but not with PSD-95 in the spines and shafts of dendrites. To disrupt the interactions with these scaffold proteins, we mutated known binding sequences for AKAP79/150 and PDZ proteins in the C terminus of Ca_V1.2-HA. Unexpectedly, the distribution pattern, the density, and the fluorescence intensity of clusters were similar for wild-type and mutant Ca_V1.2-HA, indicating that interactions with AKAP and PDZ proteins are not essential for the correct targeting of Ca_V1.2. In agreement, brief treatment with NMDA (a chemical LTD paradigm) caused the degradation of PSD-95 and the redistribution of AKAP79/150 and -actinin from dendritic spines into the shaft, without a concurrent loss or redistribution of Ca_V1.2-HA clusters. Thus, in the postsynaptic compartment of hippocampal neurons Ca_V1.2 calcium channels form signaling complexes apart from those of glutamate receptors and PSD-95. Their number and distribution in dendritic spines is not altered upon NMDA-induced disruption of the glutamate receptor signaling complex, and targeting and anchoring of Ca_V1.2 is independent of its interactions with AKAP79/150 and PDZ proteins.

Key words: L-type Ca²⁺ channels; hippocampal neurons; dendritic spines; PSD-95; -actinin; chemical LTD; immunofluorescence microscopy

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Received July 9, 2008; revised Oct. 21, 2008; accepted Nov. 11, 2008.

Correspondence should be addressed to Dr. Bernhard E. Flucher, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria. Email: bernhard.e.flucher{at}i-med.ac.at

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