The interaction of PDZ domain-containing proteins with the C termini of ␣-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors has been suggested to be important in the regulation of receptor targeting to excitatory synapses. Recent studies have shown that the rapid internalization of AMPA receptors at synapses may mediate, at least in part, the expression of long-term depression (LTD). We have previously shown that phosphorylation of Ser-880 on the AMPA receptor GluR2 subunit differentially regulated the interaction of GluR2 with the PDZ domain-containing proteins GRIP1 and PICK1. Here, we show that induction of LTD in hippocampal slices increases phosphorylation of Ser-880 within the GluR2 C-terminal PDZ ligand, suggesting that the modulation of GluR2 interaction with GRIP1 and PICK1 may regulate AMPA receptor internalization during LTD. Moreover, postsynaptic intracellular perfusion of GluR2 C-terminal peptides that disrupt GluR2 interaction with PICK1 inhibit the expression of hippocampal LTD. These results suggest that the interaction of GluR2 with PICK1 may play a regulatory role in the expression of LTD in the hippocampus. G lutamate receptors are the major excitatory neurotransmitter receptors in the central nervous system and play critical roles in synaptic plasticity, neuronal development, and neuropsychiatric disorders (1-6). Recent studies have suggested that synaptic targeting and clustering of glutamate receptors are regulated by their interaction with neuronal proteins. Specifically, the interaction of the C termini of specific N-methyl-Daspartate (NMDA) and ␣-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptor subunits with PDZ domaincontaining proteins seems to be important for the synaptic localization of the receptors (7-9). AMPA receptor GluR2͞3 subunits have been shown to interact with PDZ domains within the GRIP1, GRIP2͞ABP, and PICK1 proteins through their C-terminal four amino acids (ϪSVKI) (10-15). This interaction has been implicated in the regulation of the synaptic targeting of AMPA receptors because PICK1 coexpression with GluR2 induces clustering of GluR2 (10,13,14) and overexpression of the GluR2 C-terminal PDZ ligand disrupts AMPA receptor synaptic targeting (10).Recent studies have indicated that rapid changes in synaptic efficacy such as those that occur during long-term potentiation (LTP) and long-term depression (LTD) may be caused by rapid changes in AMPA receptor function. Although some of these effects may be mediated by modulation of AMPA receptor function by phosphorylation (16-19), rapid changes in the levels of synaptic AMPA receptors may also mediate changes in synaptic efficacy (20)(21)(22)(23)(24)(25)(26)(27). One possible mechanism for the rapid modification of the synaptic targeting of AMPA receptors is through the dynamic regulation of AMPA receptor-PDZ domain interactions. We have previously shown that phosphorylation of Ser-880 within the GluR2 C-terminal PDZ ligand differentially regulates its interaction with the PDZ domains of GRIP1 and PICK1 ...

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For cardiac tissue engineering, much attention has been given to the artificial cardiac microenvironment in which anisotropic design of scaffold and extracellular matrix (ECM) are the major cues. Here we propose poly(l-lactide-co-caprolactone) and fibroblast-derived ECM (PLCL/FDM), a hybrid scaffold that combines aligned electrospun PLCL fibers and FDM. Fibroblasts were grown on the PLCL fibers for 5-7 days and subsequently decellularized to produce PLCL/FDM. Various analyses confirmed aligned, FDM-deposited PLCL fibers. Compared to fibronectin (FN)-coated electrospun PLCL fibers (control), H9c2 cardiomyoblast differentiation was significantly effective, and neonatal rat cardiomyocyte (CM) phenotype and maturation was improved on PLCL/FDM. Moreover, a coculture platform was created using multilayer PLCL/FDM in which two different cells make indirect or direct cell-cell contacts. Such coculture platforms demonstrate their feasibility in terms of higher cell viability, efficiency of target cell harvest (>95% in noncontact; 85% in contact mode), and molecular diffusion through the PLCL/FDM layer. Coculture of primary CMs and fibroblasts exhibited much better CM phenotype and improvement of CM maturity upon either direct or indirect interactions, compared to the conventional coculture systems (transwell insert and tissue culture plate (TCP)). Taken together, our platform should be very useful and have significant contributions in investigating some scientific or practical issues of crosstalks between multiple cell types.