iTRVZ: liquid nano-platform for signal integration on the plasma membrane

Tsunoyama, T. A.; Hoffmann, C.; Tang, B.; Hirosawa, K. M.; Nemoto, Y. L.; Kasai, R. S.; Fujiwara, T.; Suzuki, K. G.; Milovanovic, D.; Kusumi, A.

doi:10.1101/2021.12.30.474523

bioRxiv · 10.1101/2021.12.30.474523

iTRVZ: liquid nano-platform for signal integration on the plasma membrane

Tsunoyama, T. A.·Hoffmann, C.·Tang, B.·Hirosawa, K. M.·Nemoto, Y. L.·Kasai, R. S.·Fujiwara, T.·Suzuki, K. G.·Milovanovic, D.·Kusumi, A.

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Abstract

Cell survival in immune-competent organisms relies on both growth and immune evasion, yet these processes have been studied as independent cellular programs. Here, using super-resolution single-molecule imaging, we identify GEM (Growth and Evasion Metastable hub), a {approx}34-nm, metastable, nano-liquid, plasma membrane hub that physically integrates receptor-type tyrosine kinase (RTK) inputs with CD59-mediated immune-evasion signaling within the same assembly. GEM is formed by LLPS-like protein clustering on PI(4,5)P2-containing raft-nanodomains. Upon concurrent RTK and CD59 stimulations, GEM recruits both receptors and downstream kinases, enabling reciprocal activation via nano-liquid confinement that supralinearly amplifies PLC{gamma}-IP3-Ca2+ and PI3K-Akt survival signaling outputs. In mice, disrupting GEM suppresses tumor growth in vivo, establishing nano-liquid GEM as an integrator that physically couples growth and CD59-mediated immune-evasion signaling for cell survival.

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Tsunoyama, T. A., Hoffmann, C., Tang, B., Hirosawa, K. M., Nemoto, Y. L., Kasai, R. S., Fujiwara, T., Suzuki, K. G., Milovanovic, D., Kusumi, A.. 2021-12-30. iTRVZ: liquid nano-platform for signal integration on the plasma membrane. https://doi.org/10.1101/2021.12.30.474523

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