| Autor: |
Wabnitz GH; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. guido.wabnitz@immu.uni-heidelberg.de., Honus S; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany., Habicht J; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany., Orlik C; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany., Kirchgessner H; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany., Samstag Y; Institute of Immunology, Section Molecular Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. |
| Abstrakt: |
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-p90 RSK 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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