Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Palmitoylation of Exocytic Proteins: Role in Membrane Compartmentalization, Intracellular Trafficking, and Function

Funder MRC (part of UKRI)
Recipient organisation University of Edinburgh
Funding £1.6M
Period Sept 2007 — Mar 2011

In plain English

AI plain-English summary

Cells release hormones and neurotransmitters by fusing tiny cargo-filled sacs with their outer membrane, a process that depends on a fatty acid called palmitate attaching to key proteins. This project addresses a fundamental gap in cell biology: how exactly palmitate regulates the proteins that drive membrane fusion. The researchers have already shown that adding palmitate to certain fusion proteins changes where they sit in the cell membrane and alters their ability to trigger release. They now want to determine precisely how palmitate controls these proteins' activity, whether the fatty acid must be dynamically added and removed for fusion to work, and how it directs proteins to specific membrane locations. This is fundamental science with no immediate practical application. Understanding how palmitate governs protein sorting and membrane fusion will provide a general paradigm for how fatty acid modifications regulate protein behaviour across many cell types. Such mechanistic knowledge could eventually inform drug design for conditions where secretion goes wrong—such as epilepsy, other brain disorders, and diabetes—but the immediate value lies in explaining a basic cellular control mechanism that has been poorly understood.

View original technical description
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.

View the original record at the funder ↗

Researchers

Luke Chamberlain (Principal Investigator)

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Original classification

Fellowship

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