신경세포 시냅스에서 Shank2, Homer 1b와 PLC-β3의 신호전달 복합체 형성

초록

Phospholipase C-β isotypes activated by G protein-coupled receptors (GPCR) and heterotrimeric G proteins carry a PSD-95/Dlg/ZO-1 (PDZ)-binding motif in their carboxyl terminus. This motif may enable PLC-β isotypes to play specific roles in GPCR signaling through interacting with PDZ-containing proteins. We identified Shank2 as a PLC-β3 binding protein, using yeast two-hybrid system in the previous study, and here we characterized the binding of PLC-β3 with Shank2. Immunoprecipitation study showed that Shank2 interacts with PDZ-binding motif of PLC-β3. Moreover, PLC-β3 was colocalized with Shank2 and Homer 1b that interacts with mGluR1 and IP3 receptor on the synapse of primary-cultured neuronal cells. Immunogold EM also showed that PLC-β3 immunoreactivity was detected at the PSD of the CA1 pyramidal neurons. In several regions of hippocampus and cerebellum, the expression pattern of Shank2 was similar to that of mGluR1, Homer 1b, and PLC-β3. These results suggest that PLC-β3, Shank2, and Homer 1b may act as active intermediates in mGluR1-mediated signal transduction by forming signaling complex in neuronal synapses.

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