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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 describ...

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Main Authors: Wabnitz, Guido H. (Author) , Honus, Sibylle (Author) , Habicht, Jüri (Author) , Orlik, Christian (Author) , Kirchgessner, Henning (Author) , Samstag, Yvonne (Author)
Format: Article (Journal)
Language:English
Published: 15 January 2021
In: Cellular and molecular life sciences
Year: 2021, Volume: 78, Issue: 7, Pages: 3543-3564
ISSN:1420-9071
DOI:10.1007/s00018-020-03744-z
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00018-020-03744-z
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Author Notes:Guido H. Wabnitz, Sibylle Honus, Jüri Habicht, Christian Orlik, Henning Kirchgessner, Yvonne Samstag
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Summary: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.
Item Description:Im Titel ist 'RSK' hochgestellt
Gesehen am 27.07.2021
Physical Description:Online Resource
ISSN:1420-9071
DOI:10.1007/s00018-020-03744-z

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