THE EXOCYST COMPLEX IN DOPAMINE TRANSPORTER TRAFFICKING

A typical day for a cell begins with communication with its surroundings by exchanging various molecules. Neurons, the brains specialised cells, communicate using chemical messengers known as neurotransmitters. On their surface, neurons carry a specific group of proteins called solute carrier 6 (SLC6) transporters, which play a crucial role in maintaining homeostasis by retrieving neurotransmitters from the extracellular environment. These proteins are also clinically significant, as they serve as targets for various drugs. Inside neurons, numerous proteins are involved in delivering these SLC6 transporters to the cell surface. A protein group called the exocyst complex facilitates this process, helping transport certain proteins from inside the cell to its surface. SLC6 transporters, such as GABA transporter 1 (GAT1) and glycine transporter 1 (GlyT1), depend on the exocyst to reach their correct location on the cell membrane. However, it remains unclear whether other SLC6 transporters also rely on the exocyst for proper placement. Although some proteins can reach the cell surface without the exocysts assistance, their transport is often less efficient or disrupted. Correct localisation of SLC6 transporters is particularly important for cell function, especially in neurons, where misplacement may have unknown consequences. Missense mutations (small changes in the genetic code) in exocyst components have been linked to various disorders. It remains uncertain whether chemical treatments or pharmacochaperoning could repair these faulty components. This research focuses on identifying which SLC6 transporters depend on the exocyst and understanding how disruptions in this machinery affect their function and overall neuronal health. Advanced cell culture techniques and fruit fly (Drosophila melanogaster) models will be utilised in this study. The findings will provide insights into the physiological role of the exocyst complex in the membrane targeting of SLC6 transporters and explore whether small chemical molecules can restore the function of exocyst component mutants.