Association of CaV1.3 L-Type Calcium Channels with Shank

• DOI: 10.1523/jneurosci.4554-04.2005
• Publication Date: 2005-02-02T20:40:28Z
• Authors: Hua Zhang; Anton Maximov; Yu Fu; Fang Xu; Tie-Shan Tang; Tatiana Tkatch; D. James Surmeier; Ilya Bezprozvanny
• Keywords: Cav1.2; PDZ domain; Postsynaptic density; R-type calcium channel

Neurons express multiple types of voltage-gated calcium (Ca 2+ ) channels. Two subtypes neuronal L-type Ca channels are encoded by V 1.2 and 1.3 pore-forming subunits. Both 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 rat brain cDNA library with the C-terminal bait 1.3a (long splice variant) channel subunit, we isolated clones postsynaptic adaptor protein Shank. We demonstrated a specific association termini, but not Shank domain in vitro . further that proline-rich region present termini subunit binds to Src homology 3 domain. established localized locations cultured hippocampal neurons. By expressing epitope-tagged recombinant cultures, presence Shank-binding motifs sequence is both necessary sufficient for synaptic clustering experiments dominant-negative peptides dihydropyridine-resistant mutants, an importance motif phosphorylated cAMP response element-binding (pCREB) signaling Our results directly link macromolecular complex formed other modular proteins density provide novel information about role played pCREB signaling.