Ziff Laboratory - Research

	SPINE AND SYNAPSE MORPHOGENESIS In hippocampal pyramidal neurons and other neuron types, glutamatergic synapses are located at the heads of spines, which are specialized dendritic structures that compartmentalize glutamatergic synapse activity. (Figure) AMPAR Scaffolds: AMPARs are anchored at synapses through interaction with specialized scaffolds. We study the specialized scaffolds, ABP and GRIP, which are multi-PDZ proteins that bind GluR2 and Eph receptors and Ephrins as well as other synaptic proteins (Srivastava, et al, 1998 (PDF)). ABP and GRIP connect GluR2 to the cadherin cell adhesion protein complex through binding to Neural Plakophilin Related ARM Protein (NPRAP; delta catenin), a cadherin-associated protein (Silverman et al., 2007 (PDF)). Notably, we find that NPRAP can also induce actin polymerization and contribute to spine morphogenesis. (Diagram). PSD Proteins: The postsynaptic density is a specialize complex of cytoskeletal, and regulatory proteins found at the heads of spines (reviewed by Ziff, 1997 (PDF)). The PSD functions in anchoring AMPARs at synapses and contributes to the establishment of spine morphology. We have used mass spectrometry to identify components of the PSD (Jordan et al, 2004 (PDF)). We study regulatory functions of PSD components, including AIDA (Jordan et al., 2007 (PDF)) and the ARF GEF, IQsec, whose expression stimulates spine maturation. (Figure) 1. AMPA RECEPTOR TRAFFICKING AND THE CONTROL OF SYNAPSE STRENGTH. 2. SPINE AND SYNAPSE MORPHOGENESIS 3. NEUROLOGICAL DISEASE

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