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PSD-95: dynamic localization of PSD-95 and glutamate receptors at postsynaptic sites
Published on July 31, 2022 43 min
Other Talks in the Series: Synapses, Neurotransmitters and Receptor Channels
Postsynaptic scaffold proteins in health and disease
- Dr. Jonathan Hanley
- University of Bristol, UK
PSD-95: structural aspects of PDZ domain binding
- Prof. Johannes Hell
- University of California, Davis, USA
Molecular basis of NMDA receptor functional diversity
- Prof. Jon Johnson
- University of Pittsburgh, USA
AMPA-receptors and fast synaptic transmission in the brain
- Prof. Stuart Cull-Candy
- University College London, UK
My name is Johannes Hill. I am Professor of Pharmacology at University of California, Davis. In addition, I'm vice chair of pharmacology for academic development, the Departmental Mentoring Director and the director of our NH funded T32 training program in pharmacology. This training program focuses on drug discovery and development. PSD-95, is one of the most critical structural proteins that organizes the postsynaptic site of synopsis in some mammalian brain. This presentation will provide an in-depth overview of its structure and function, starting with the discovery that it interacts with postsynaptic glutamate receptors.
My research interests are focused on the structural and functional organizational of the postsynaptic site of glutamatergic synopsis. We use biochemistry, including structural analysis of proteins, cell biology including super-resolution microscopy. Electrophysiology including recording of excitatory postsynaptic currents or EPCs, mini EPCs in single channels. Behavior analysis, which includes memory and attention testing. Framing key findings in historical and methodological context will elucidate the discovery process for people new to this field, and perhaps makes this presentation inspiring and informative, especially for my younger colleagues.
Here's an overview of the learning goals. First, I will introduce the basics of neurotransmission and glutamate receptors. Then I will provide an overview of some earlier work that defined interactions of PSD-95 with glutamate receptors. This overview will be followed by a detailed description of the structural aspects of binding of the PDZ domains of PSD-95 to its target proteins. These details remain highly relevant and are widely applicable to literally hundreds of such interactions. These biochemical aspects will be followed by the description of how PSD-95 itself is anchored at postsynaptic sites and then up out some specific functions of PSD-95 beyond glutamate receptor functions. There is a second separate talk that is focused on the structural aspects of the PDZ domain interactions. As typical for Henry Stewart talks, most details are taken from my own work, but I will supplement with some additional work by others and provide appropriate citations when indicated.