NPP Seminar: Dr Ingo Greger, MRC Laboratory of Molecular Biology, Cambridge

Academic Host: Stuart Cull-Candy

Abstract: AMPA glutamate receptors (AMPARs) mediate fast excitatory neurotransmission throughout the brain, and are central players in various forms of synaptic plasticity that underlies learning. In addition to four core subunits (GluA1-4), an array of auxiliary subunits render AMPAR response properties uniquely versatile, tuned to the function of a given circuitry. These assemble with the receptor core in various stoichiometries, and in a brain-region specific fashion.

Recent cryo-EM structural data, combined with functional studies, have started to shed light on the arrangement of both, core and auxiliary subunits. Hence, despite tremendous versatility, unique to AMPA-type glutamate receptors, organizing principles are beginning to emerge. In this talk, I will discuss our current understanding of how the predominant GluA2-containing receptors are organized, with a focus on hippocampal pyramidal AMPA receptors. I will then introduce new work on a major Ca2+ permeable AMPA receptor, the GluA1 homomer (associated with four TARP auxiliary subunits), which plays a role in the induction of long-term potentiation (LTP), and is associated with various diseases. Our GluA1 cryo-EM structures shed light on the unique gating modes of this receptor, which markedly differ from those containing GluA2, and may safeguard neurons from toxic Ca2+ influx.