Robert Edwards

Research Interests

We are interested in the recycling of neurotransmitter and ions at the nerve terminal and its role in neuropsychiatric disease.

Research Summary

Synaptic transmission involves the regulated exocytosis of specialized secretory vesicles filled with transmitter. Since classical transmitters are made in the cytoplasm, release by exocytosis thus requires transport into secretory vesicles. We have identified three distinct protein families responsible for this activity, one for monoamines and acetylcholine, a second for the inhibitory transmitter GABA and a third family dedicated to the excitatory transmitter glutamate. In the process, the work has implicated vesicular transport in the neural degeneration associated with Parkinson's disease. We have also identified additional proteins involved in the glutamine-glutamate cycle that regenerates the glutamate required for both excitatory and inhibitory transmission. We now wish to understand the biophysical and structural basis of neurotransmitter transport, its regulation by membrane trafficking and other mechanisms, and its role in synaptic transmission.

Selected Publications

Chaudhry, F.A., Krizaj., D., Larsson, P., Reimer, R.J., Wreden, C., Storm-Mathisen, J., Copenhagen, D., Kavanaugh, M., Edwards, R.H. 2001. Coupled and uncoupled proton movement by amino acid transport system N. EMBO J. 20, 7041-7051.

Fremeau, R.T. Jr., Burman, J., Qureshi, T., Tran, C.H., Proctor, J., Johnson, J., Zhang, H., Sulzer, D., Copenhagen, D.R., Storm-Mathisen, J., Reimer, R.J., Chaudhry, F.A., Edwards, R.H. 2002. The identification of vesicular glutamate transporter 3 suggests novel modes of signalling by glutamate. Proc. Natl. Acad. Sci. USA 99, 14488-14493.

Fremeau, R.T. Jr., Kam, K., Qureshi, T., Johnson, J., Copenhagen, D.R., Storm-Mathisen, J., Chaudhry, F.A., Nicoll, R.A., Edwards, R.H. 2004. Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304, 1815-1819.

Li, H., Waites, C.L., Park, J., Dobryy, Y. and Edwards, R.H. 2005. Vesicular monoamine transporter 2 targets directly to large dense core vesicles during biosynthesis and defines a novel regulated secretory pathway in neurons. Neuron 48, 619-33.

Fortin, D.L., Nemani, V.M., Voglmaier, S.M., Anthony, M.D., Ryan, T.A., Edwards, R.H. 2005. Neural activity controls the synaptic accumulation of -synuclein. J. Neurosci. 25, 10913-10921.