NA - The role of exocyst protein/glutamate receptor interactions in postsynaptic receptor trafficking

The concept of excitotoxicity covers the process of harmfull overstimulation of glutamate receptors in neurons. It is integral to neurodegenerative diseases such as stroke, seizures, brain trauma, etc. We have recently started a new EU funded collaborativ e project ("GRIPANNT") on the role of glutamate receptor interacting proteins in mediating damaging intracellular signals upon glutamate receptor overstimulation. We are focusing our work on AMPA receptors (a well characterized glutamate receptor) and int eracting proteins NEEP21 and PICK1, together with collaborators in Bristol and Lausanne. At Stanford University ten years ago, I worked together with a fellow postdoc (Shu Chan Hsu) on the exocyst or sec6/sec8 complex. This complex, with diverse roles in membrane traffick and vesicle targeting, had recently been discovered in yeast but we were the first to establish its existence in mammals, highly expressed in neurons (Hsu et al., 1996; Vik-Mo et al., 2003). I later left this field, but the exocyst compl ex has recently been shown to have roles also in postsynaptic glutamate receptor trafficking (Sans et al., 2003; Gerges et al., 2005). It would then, in the context of my present focus on glutamate receptor interactions as well as the strategic focus of m y institution (The Medical Faculty, University of Oslo), be very interesting to take up again work on the exocyst complex. I would be interested this time on focusing on its function in regulating the postsynaptic membrane expression of glutamate receptor s, and possibly in excitotoxicity. To my knowledge, however, there are no established European players in this field, and Dr. Hsu's lab is still the only one who has raised functional antibodies against exocyst proteins. We need to establish a separate co llaboration with Dr. Hsu, independently of the ongoing European partnership.