PT  - JOURNAL ARTICLE
AU  - Hua Zhang
AU  - Anton Maximov
AU  - Yu Fu
AU  - Fang Xu
AU  - Tie-Shan Tang
AU  - Tatiana Tkatch
AU  - D. James Surmeier
AU  - Ilya Bezprozvanny
TI  - Association of Ca<sub>V</sub>1.3 L-Type Calcium Channels with Shank
AID  - 10.1523/JNEUROSCI.4554-04.2005
DP  - 2005 Feb 02
TA  - The Journal of Neuroscience
PG  - 1037--1049
VI  - 25
IP  - 5
4099  - http://www.jneurosci.org/content/25/5/1037.short
4100  - http://www.jneurosci.org/content/25/5/1037.full
SO  - J. Neurosci.2005 Feb 02; 25
AB  - Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by CaV1.2 and CaV1.3 pore-forming subunits. Both CaV1.2 and CaV1.3 subunits contain class I PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-binding consensus at their C termini. In yeast two-hybrid screen of rat brain cDNA library with the C-terminal bait of CaV1.3a (long C-terminal splice variant) L-type Ca2+ channel subunit, we isolated multiple clones of postsynaptic adaptor protein Shank. We demonstrated a specific association of CaV1.3a C termini, but not of CaV1.2 C termini, with Shank PDZ domain in vitro. We further demonstrated that the proline-rich region present in C termini of CaV1.3a subunit binds to Shank Src homology 3 domain. We established that CaV1.3a and Shank localized to postsynaptic locations in cultured rat hippocampal neurons. By expressing epitope-tagged recombinant CaV1.3 subunits in rat hippocampal neuronal cultures, we demonstrated that the presence of Shank-binding motifs in CaV1.3a sequence is both necessary and sufficient for synaptic clustering of CaV1.3 L-type Ca2+ channels. In experiments with dominant-negative peptides and dihydropyridine-resistant CaV1.3a mutants, we demonstrated an importance of Shank-binding motif in CaV1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons. Our results directly link CaV1.3 neuronal L-type Ca2+ channels to macromolecular signaling complex formed by Shank and other modular adaptor proteins at postsynaptic density and provide novel information about the role played by CaV1.3 L-type Ca2+ channels in pCREB signaling.