Cathepsin X-mediated beta 2 integrin activation results in nanotube outgrowth

• Published in: Cellular and molecular life sciences : CMLS 2009-03, Vol.66 (6), p.1126-1134
• Main Authors: Obermajer, N, Jevnikar, Z, Doljak, B, Sadaghiani, A M, Bogyo, M, Kos, J
• Format: Article
• Language: English
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-009-8829-8

Membrane nanotubes were recently described as a new principle of cell--cell communication enabling complex and specific messaging to distant cells. Calcium fluxes, vesicles, and cell-surface components can all traffic between cells connected by nanotubes. Here we report for the first time the mechanism of membrane nanotube formation in T cells through LFA-1 (CD11a/CD18; alpha L beta 2) integrin activation by the cysteine protease cathepsin X. Cathepsin X is shown to induce persistent LFA-1 activation. Cathepsin X-upregulated T cells exhibit increased homotypic aggregation and polarized, migration-associated morphology in 2D and 3D models, respectively. In these cells, extended uropods are frequently formed, which subsequently elongate to nanotubes connecting T lymphocytes. Our results demonstrate that LFA-1 activation with subsequent cytoskeletal reorganization induces signal transmission through a physically connected network of T lymphocytes for better coordination of their action at various stages of the immune response.