Description:

William N. Green, Ph.D., is a professor in the department of Neurobiology at the University of Chicago

Presentation Abstract: PSD-95 and SAP97 are homologous scaffold proteins with different N-terminal domains containing either a palmitoylation site (PSD-95) or an L27 domain (SAP97). In postsynaptic densities (PSDs) of glutamatergic synapses, both proteins are potential scaffolds for AMPA and NMDA-type glutamate receptors. I will describe data combining FRET and electron microscopy to assess PSD-95 and SAP97 conformation and orientation in PSDs, along with in vitro assays of PSD-95 palmitoylation and its interactions with AMPARs and NMDARs. In addition, I will describe data combining several super-resolution microscopy techniques, PALM, STORM and FIONA, to assay the dynamics and distributions of AMPA and  NMDA receptors relative to post-synaptic densities at synapses. Altogether our results suggest that PSD-95 and SAP97 conformation and orientation play a role in how NMDARs and AMPARs are organized and segregated within PSDs, and how they are differentially regulated during synaptic plasticity. We propose that PSD-95 and SAP97 together organize more stable NMDAR nanodomains that limit access of palmitoylation/depalmitoylation enzymes, while PSD-95 without SAP97 organize more dynamic AMPAR nanodomains that are more accessible to these enzymes.