TY - JOUR T1 - Stable Membrane Expression of Postsynaptic Ca<sub>V</sub>1.2 Calcium Channel Clusters Is Independent of Interactions with AKAP79/150 and PDZ Proteins JF - The Journal of Neuroscience JO - J. Neurosci. SP - 13845 LP - 13855 DO - 10.1523/JNEUROSCI.3213-08.2008 VL - 28 IS - 51 AU - Valentina Di Biase AU - Gerald J. Obermair AU - Zsolt Szabo AU - Christophe Altier AU - Juan Sanguesa AU - Emmanuel Bourinet AU - Bernhard E. Flucher Y1 - 2008/12/17 UR - http://www.jneurosci.org/content/28/51/13845.abstract N2 - In neurons L-type calcium currents contribute to synaptic plasticity and to activity-dependent gene regulation. The subcellular localization of CaV1.2 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 CaV1.2 in the postsynaptic compartment of glutamatergic neurons. Double-immunofluorescence labeling of hippocampal neurons transfected with external HA epitope-tagged CaV1.2 demonstrated that clusters of membrane-incorporated CaV1.2-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 CaV1.2-HA. Unexpectedly, the distribution pattern, the density, and the fluorescence intensity of clusters were similar for wild-type and mutant CaV1.2-HA, indicating that interactions with AKAP and PDZ proteins are not essential for the correct targeting of CaV1.2. In agreement, brief treatment with NMDA (a chemical LTD paradigm) caused the degradation of PSD-95 and the redistribution of AKAP79/150 and α-actinin from dendritic spines into the shaft, without a concurrent loss or redistribution of CaV1.2-HA clusters. Thus, in the postsynaptic compartment of hippocampal neurons CaV1.2 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 CaV1.2 is independent of its interactions with AKAP79/150 and PDZ proteins. ER -