Anchoring to the cytoskeleton via PSD

Anchoring to the subsynaptic cytoskeleton can be considered a final step in the process of postsynaptic targeting of glutamate receptors. By binding to cytoskeletal elements, a scaffold protein such as PSD-95 can indirectly connect NMDA receptors to the cytoskeleton. 

Members of the PSD-95 family of proteins have been shown to bind in vitro to band 4.1, an actin/spectrin-binding protein (Lue et al., 1994, 1996 Marfatia et al., 1996). Such an interaction has the potential to link NMDA receptors indirectly to F-actin, which is the predominant cytoskeleton in dendritic spines. Whether band 4.1 or other members of the ezrin-radixin-moesin (ERM) family of actin-binding proteins play a role in postsynaptic anchoring of NMDA receptors and PSD-95 is unknown. 

NMDA receptors contain the essential NRl subunit in addition to the NR2 subunits that bind to PSD-95 family proteins. The cytoplasmic tail of NRl undergoes considerable alternative splicing (Hollmann et al., 1993). Although it does not bind to PSD-95, the C-terminal cytoplasmic tail of NRl does interact with several other cytoplasmic proteins (Fig. 2). Like NR2-PSD-95 interactions, these NRl-mediated interactions may play a role in synaptic targeting of NMDA receptors and NMDA receptor-associated signaling proteins. 

The Cl exon segment of the NRl tail is not required for calcium-dependent inactivation of NMDA receptors despite binding calmodulin, but it does contain several protein kinase C 

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