PLC gamma 1 promotes phase separation of T cell signaling components
LH Zeng and I Palaia and A Saric and XL Su, JOURNAL OF CELL BIOLOGY, 220, e202009154 (2021).
The T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here, we report that phospholipase C gamma 1 (PLC gamma 1) promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLC gamma 1 directly cross-links LAT through its two SH2 domains. PLC gamma 1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation. Intriguingly, a nonmonotonic effect of PLC gamma 1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLC gamma 1 in promoting phase separation of the LAT complex and TCR signal transduction.
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