Cathepsin X-mediated beta2 integrin activation results in nanotube outgrowth.
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.
Obermajer
N
N
Department of Pharmaceutical Biology, Faculty of Pharmacy, Ljubljana, Slovenia. natasa.obermajer@ffa.uni-lj.si
Jevnikar
Z
Z
Doljak
B
B
Sadaghiani
A M
AM
Bogyo
M
M
Kos
J
J
D056657:Cathepsin K; D002403:Cathepsins / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D015854:Up-Regulation / Q000502:physiology
D016169:Lymphocyte Function-Associated Antigen-1; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K