Podosomes are actin-rich structures found on macrophages and dendritic cells (DCs), among other cell types. Podosomes are able to degrade the underlying matrix and so may contribute to the migratory ability of DCs, which need to cross matrix barriers in order to fulfil their function in antigen presentation. Podosomes are rapidly disassembled in maturing DCs, which has been shown to be mediated by Toll-like-receptor (TLR) signalling. Integrins are also important components of podosomes, but their exact role is not clear owing to the fact that, in most cells, a number of integrins are found in podosomes. In this work (p.4213), Colin Watts and co-workers first show that DCs from the bone marrow and spleen of β2-integrin-null mice show a striking reduction in podosome formation compared to wild-type DCs. The authors then address the underlying mechanisms of β2 integrin in podosome formation by expressing different mutants in these knockout cells. They find that three cytoplasmic integrin motifs, known to bind to talin and kindlins, are crucial for podosome formation and identify amino acids required for TLR-mediated podosome disassembly. In addition, the authors show that podosome-localised integrins form a long-lived framework that supports repeated actin core formation events. Therefore, in addition to providing new insights into the mechanisms of podosome dynamics, this work also establishes a valuable experimental system to further dissect the role of integrins in podosomes.

© 2014. Published by The Company of Biologists Ltd
2014