LFA-1 cluster formation in T-cells depends on l-plastin phosphorylation regulated by P90RSK and PP2A


The integrin LFA-1 is crucial for T-cell/ APC interactions and sensitive recognition of antigens. Precise nanoscale organization and valency regulation of LFA-1 are mandatory for an appropriate function of the immune system. While the inside-out signals regulating the LFA-1 affinity are well described, the molecular mechanisms controlling LFA-1 avidity are still not fully understood. Here, we show that activation of the actin-bundling protein l-plastin (LPL) through phosphorylation at serine-5 enables the formation of clusters containing LFA-1 in high-affinity conformation. Phosphorylation of LPL is induced by an nPKC–MEK–p90RSK pathway and counter-regulated by the serine–threonine phosphatase PP2A. Interestingly, recruitment of LFA-1 into the T-cell/APC contact zone is not affected by LPL phosphorylation. Instead, for this process, activation of the actin-remodeling protein cofilin through dephosphorylation is essential. Together, this study reveals a dichotomic spatial regulation of LFA-1 clustering and microscale movement in T-cells by two different actin-binding proteins, LPL and cofilin.

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This work was supported by Grants from the German research foundation (SA 393/3-4, TRR156-B4 and INST 114089/31-1 FUGG).

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GHW and YS designed the study; SH, CO, JH, and HK performed experiments; YS raised funding; GHW, CO, SH and YS wrote the manuscript.

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Correspondence to Guido H. Wabnitz.

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Wabnitz, G.H., Honus, S., Habicht, J. et al. LFA-1 cluster formation in T-cells depends on l-plastin phosphorylation regulated by P90RSK and PP2A. Cell. Mol. Life Sci. (2021). https://doi.org/10.1007/s00018-020-03744-z

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  • Immune synapse
  • LPL
  • T-cells
  • LFA-1 cluster
  • PP2A
  • p90RSK