Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission in the vertebrate brain, and are critical for normal brain function and development. All three iGluR subfamilies (i.e. AMPA-type, kainate-type and NMDA-type) assemble as tetramers of four homologous subunits. We have developed a method, based on atomic force microscopy (AFM) imaging, for determining the arrangement of subunits within the various receptors. For example, we have recently shown that while the GluA1/GluA2 AMPA receptor assembles with an alternating (i.e. 1/2/1/2) subunit arrangement, the GluN1/GluN2A NMDA receptor adopts an adjacent (i.e. 1/1/2/2) arrangement. We now wish to study the nature of the interaction of the iGluRs with various ‘accessory proteins’, such as TARPs, cornichons, Neto-1 and -2, and CKAMP-44. These proteins affect the assembly, trafficking and function of the iGluRs, and so play critical roles in excitatory neurotransmission. The project will address the subunit specificity of the interactions between the receptors and their accessory subunits and the architecture of the complexes fomed between them. Techniques to be used will include tissue culture, cell transfection, SDS-PAGE, immunoblotting and AFM.
- Suzuki, Y., Goetze, T.A., Stroebel, D., Balasuriya, D., Yoshimura, S.H., Henderson, R.M., Paoletti, P., Takeyasu, K. and Edwardson, J.M. (2013) Visualization of structural changes accompanying activation of NMDA receptors using fast-scan AFM imaging. J. Biol. Chem. 288, 778-784
- Balasuriya, D., Goetze, T.A., Barrera, N.P., Stewart, A.P., Suzuki, Y. and Edwardson, J.M. (2013) AMPA and NMDA receptors adopt different subunit arrangements. J. Biol. Chem. 288, 21987-21998
- Balasuriya, D., Stewart, A.P. and Edwardson, J.M. (2013) The sigma-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor. J. Neurosci. 33, 18219-18224