Palmitoylation Of Exocytcic Proteins: Role In Membrane Compartmentalisation, Intracellular Trafficking, And Function

Certain cells contain small sacs or vesicles filled with important cargo, such as hormones or neurotransmitters. Appropriate stimuli trigger the fusion of these vesicles with the cell membrane, resulting in cargo secretion from the cell. A large number of proteins are required for membrane fusion, and it is essential to determine how these various proteins are regulated. Interestingly, we have shown that the attachment of palmitate (a fatty acid) to certain proteins modifies their localisation in the cell membrane and regulates their ability to support membrane fusion. This proposal will precisely determine how palmitate addition regulates the activity of proteins that mediate membrane fusion, and identify whether dynamic addition/removal of palmitate is important for fusion activity. Furthermore, we will determine how palmitate regulates the sorting of proteins to specific locations in the cell. These analyses will provide valuable and novel information on the regulation of membrane fusion by palmitate, and will also serve as an important paradigm to understand how palmitate regulates the sorting and membrane distribution of proteins in general. The results generated from this study will hopefully contribute to the design of treatments for conditions such as epilepsy and other brain disorders, and metabolic disorders such as diabetes.