Molecular architecture of the postsynaptic membrane
The ‘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.
- Frank, R., Komiyama, N., Ryan, T., Zhu, F., O’Dell, T., Grant, S. (2016)
NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation.
Nature Communications 7:11264:
- Frank, R., Zhu, F., Komiyama, N., Grant, S. (2017)
Hierarchical organisation and genetically separable subfamilies of PSD95 postsynaptic supercomplexes
Journal of Neurochemistry, In press
- Frank, R. and Grant, S. (2017)
Supramolecular organization of NMDA receptors and the postsynaptic density.
Curr Opin Neurobiol 45: 139-147