Studying ER to synapse trafficking of neuronal receptors to attempt to understand both the spatial segregation and the effect of synaptic activity on trafficking through the secretory pathway (360G-Wellcome-102388_Z_13_A)

The overall theme of this project is to visualize the synchronous trafficking of multiple di fferent Neuronal receptors through the Secretory Pathway of primary Neurons. Neuronal receptors carry out their function at the Synapse but begin their journey whenthey are threaded into the lumen of the Endoplasmic Reticulum (ER). From the ER receptors journey to the Golgi to be post-translationally modified before trafficking to the synapse to fulfil their role in Synaptic transmission. The unique properties of Neurons and the still outstanding fundamental gaps in knowledge of Neuronal receptor trafficking through the Secretory Pathway are to be investigated. 1.Investigate the route that Golgi resident enzymes take to traffic to Golgi outposts from the ER. 2.Visualize multiple receptors (Heteromers or different classes of receptor) trafficking through the cell. 3.What effect does synaptic activity or lack of have upon Neuronal receptors at different points of receptor trafficking from the ER to the cell surface. 4.Combining RUSH with photoswitchable fluorescent proteins to understand the spatial restriction of the Secretory Pathway at Synaptic sites 5. Investigate disease causing mutations that effect domains of Neuronal receptors involved in trafficking.