Ingo Greger

Ingo Greger, Neurobiology Division, MRC Laboratory of Molecular Biology, UK

Title

Mechanisms underlying activation and modulation of AMPA receptor complexes

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 needs 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. This information will ultimately allow us to decipher the activation mechanisms underlying synaptic AMPAR responses. In this talk I will discuss our current understanding of AMPAR organization, and latest insights into its modulation by prominent auxiliary subunits. Lastly, I will discuss recent structural insights into the unique conformational dynamics of GluA1, a receptor which selectively contributes to various forms of synaptic plasticity, and its unexpected deviation from GluA2-containing AMPARs.

Biosketch

Ingo Greger obtained his PhD in 1998 fromthe University of Oxford (UK), where he investigatedmechanisms of gene expression in NickProudfoot’s lab, using yeast as a model system. In 1999 he moved to Ed Ziff’s lab at theNYU School of Medicine & HHMI. In Ed’s lab he started his work onAMPA receptors, investigating their biogenesis and trafficking mechanisms from the endoplasmic reticulum. Back in the UK, he continuedhis work on glutamate receptors whilst a RoyalSociety fellow at the MRC LMB in Cambridge,from 2003-2006. At the LMB he added structural approaches (X-ray crystallography) and patch-clamp electrophysiology to his tool box.

He is currently a senior MRCinvestigator at the LMB. His lab studiesAMPA receptor operation at various levelsof complexity, using a combination of structural, functional and imaging approaches. His ultimate aim is to understand AMPAR receptor signalling at the atomic level, and how glutamate receptor regulation at synapses contributes to learning.

Website: https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/ingo-greger