| First Author | West MA | Year | 2008 |
| Journal | J Cell Biol | Volume | 182 |
| Issue | 5 | Pages | 993-1005 |
| PubMed ID | 18762577 | Mgi Jnum | J:138782 |
| Mgi Id | MGI:3806391 | Doi | 10.1083/jcb.200801022 |
| Citation | West MA, et al. (2008) TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent. J Cell Biol 182(5):993-1005 |
| abstractText | Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin-rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling-induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor alpha-converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this 'sheddase' in regulating an actin-based structure. |
