An extra lipid unleashes calcium channels

T cells are white blood cells involved in the adaptive immune response. To properly fight pathogens, they need to connect with antigen-presenting cells and form a structure called the immune synapse. This connection requires the correct localization of ORAI1 calcium channels at the immune synapse to make the immune response possible. Understanding how ORAI1 channels are regulated is of crucial importance, as their overactivity leads to severe diseases still lacking specific treatments, such as myopathies and inflammations of the pancreas.

Small change, big effects

In their recent study in eLife, scientists from the laboratory of Prof. Nicolas Demaurexin collaboration with other scientists from the laboratory of Prof. van der Goot, have discovered the key role of a post-transcriptional change in the ORAI1 calcium channels. Researchers have evidenced that the lack of a single lipid at a specific position, i.e. lack of S-acylation, was enough to hinder channel localization at the immune synapse and hamper T-cell activity.

ORAI channels are observed in green in T cells which upon interaction with an antigen presenting cell (magenta) accumulate in the immune synapse (white zone, left movie). In mutant T cells lacking ORAI1 S-acylation there is less immune synapse formation and ORAI1 is accumulated in the back of the immune synapse  (right movie) © supplementary data from Carreras-Sureda et al. eLife 2021.

What’s next?

The research team is now investigating if S-acylation might also impact the other players of calcium fluxes, with a particular focus on the STIM protein. They aim also to determine its role in other physiological processes, such as muscle differentiation.

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