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Molecular Mechanisms of Synaptic Regulation

Edward Ziff Ph.D.
Professor

Department of Biochemistry

 
Research Summary
Our lab studies the molecular mechanisms which regulate synaptic transmission at excitatory synapses. We focus on two ion channels, the AMPA and the NMDA type glutamate receptors. These receptors are multisubunited pores that admit cations into the postsynaptic cell when stimulated by glutamate. AMPA receptors function in fast excitatory transmission while NMDA receptors function in altering synaptic architecture and transmission strength. Both receptor types are composed of integral membrane protein subunits that project domains outside the cell and into the cytoplasm. The cytoplasmic domains associate with binding proteins that serve as attachment sites to the cytoskeleton or to regulatory proteins (such as kinase or phosphatases) that modify receptor activity. We have cloned proteins which associate with the cytoplasmic tail of the GluR2 AMPA type glutamate receptor subunit and are studying the role of these binding factors in receptor control. One protein that binds to GluR2 is the chaperone, NSF. A second protein is AMPA Receptor Binding Protein (ABP). ABP may form a cytoplasmic scaffold that binds receptors at the synapse. We are testing a model that NSF regulates the attachment of GluR2 to ABP and other cytoplasmic factors. We are studying the role of the NMDA receptor in the control of the AMPA receptor. Our goal is to obtain a molecular view of changes in synaptic signaling induced by neuron activity.
 
Related Images
Image 1 Dr. Ziff's laboratory studies proteins such as PSD95/SAP90 and PSD96 which bind to the cytoplasmic face of glutamate receptors and regulate their function.
 
Research Information
Research Interests Molecular Mechanisms of Synaptic Regulation
Research Keywords synapse, ion channel, glutamate receptor, neurobiology
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