Novel "SwissKASH" tool visualizes palmitoylation in living cells

A new tool has been developed to visualize the process of palmitoylation, a post-translational modification that allows peripheral membrane proteins (pmp) to bind to cell membranes, in living cells

Not only will the tool provide greater insight into how palmitoylation works, but it may also open up its uses for therapeutic purposes

The research team has shown that, contrary to previous thinking, palmitoylation can occur not only in the Golgi apparatus (the usual location for protein processing and delivery), but also in the plasma membrane

The work is published inan article in the journal Nature Communications , " Local and substrate-specific S-palmitoylation determines subcellular localization of Gαo

Palmitoylation involves the introduction of fatty acids into certain proteins, enabling them to bind to cell membranes

Dr Gonzalo Solis, Senior Research Fellow at the Department of Cell Physiology and Metabolism at the Université de Genève (UNIGE), explained: "In fact, these proteins are produced in the cytoplasm (the cell fluid) and then 'swim' to the Golgi apparatus, where they are modified, They are then transported to where they need to act

To test this hypothesis, the research team used a new approach to focus on Gαo proteins, which are normally located in the plasma membrane and Golgi apparatus

More specifically, they describe "segmentation of the Gαo-α subunit of the heterotrimeric graphene oxide protein into the PM and Golgi, independent of Golgi-to-PM trafficking

"We brought palmitoylase to a completely different area of ​​the cell, the nuclear membrane," explains Solis

A new tool, the S-palmitoylated outer nuclear membrane assay (SwissKASH), probes the substrate specificity of PATs in intact cells

This discovery paves the way for innovative drug discovery strategies that can very precisely target the membrane binding of oncogenic proteins to enhance their activity

Some peripheral membrane proteins, especially Gα subunit proteins and RAS proteins, are prone to mutation and thus have aggressive oncogenic potential

"Thus, inhibiting the enzyme that induces palmitoylation, and preventing the oncogenic protein from binding to the plasma membrane, could reduce its pathogenicity," Solis noted