Rene Frank

René Frank

Molecular architecture of the postsynaptic membrane
rene@mrc-lmb.cam.ac.uk

Artistic impression of a genetically modified mouse synapseThe ‘wiring’ of neuronal circuits in the mammalian brain is mediated by synapses, which are responsible for processing and storing information. We are interested in understanding the native molecular architecture of synapses with a particular focus on postsynaptic membranes that contain N-methyl D-aspartic acid receptors (NMDARs).

NMDARs mediate Ca2+-dependent signalling, acting in concert with a complex repertoire of synaptic proteins to initiate synaptogenesis and various forms of synaptic plasticity. We are using mouse genetics in combination with novel biochemical methods, fluorescence imaging, and cryo-electron tomography. This integrated approach allows us to investigate the postsynaptic membrane directly and test its molecular mechanisms in vivo.

Allied to the basic biology are key questions regarding synapses in Alzheimer’s disease (AD). Particularly, what signalling mechanisms are involved in the loss of glutamatergic synapses in AD, and how these are linked to Aβ and tau pathologies? To address these questions we are using genetically engineered mice and in vivo protein labelling methods.

Anatomically restricted expression of NMDAR-Kir2.3 ion channel-channel supercomplexes and their dependence on PSD95Cryo-electron microscopy of purified postsynaptic membranes

Selected Papers