A unifying model of T-cell signaling protein condensates in reconstitution experiments
The formation of condensates by the Linker for the Activation of T-cells (LAT) is a key signal gating and amplification step in the T-cell receptor signaling pathway. LAT condensation is challenging to study in-vivo and is therefore often investigated using reconstitution experiments. While these experiments recapitulate key aspects of LAT condensation, they also exhibit some puzzling features.…
The formation of condensates by the Linker for the Activation of T-cells (LAT) protein is a crucial step in the T-cell receptor signaling pathway. However, studying LAT condensation in living cells is difficult, leading researchers to use reconstitution experiments. These experiments capture many aspects of LAT condensation but also display some perplexing characteristics. The article delves into the mechanisms behind these phenomena using two distinct models.
The first model, a Smoluchowski aggregation model, elucidates the origin of the time delay before condensation. This delay is attributed to a low effective binding probability between LAT monomers. The second model proposes a field-theoretic approach, which successfully reproduces all condensate morphologies observed in experiments. This model demonstrates that these diverse morphologies can be generated from fundamental dynamics, which are influenced by variations in experimental conditions.
This new understanding not only resolves existing questions about LAT condensation but also offers a unified framework for comprehending the condensation process in other multivalent membrane proteins. These proteins include EGFR, FGFR2, and nephrin, indicating the broad applicability of this research.
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