Podosomes are dynamic actin-rich structures that are able to locally degrade the matrix through recruitment of matrix-lytic enzymes; this allows macrophages to cross tissue barriers and navigate through dense extracellular matrix. The podosome core has been shown to contain branched actin filaments that are nucleated by Arp2/3, but recent evidence also suggests the presence of unbranched filaments in podosomes. In their work on page , Stefan Linder and colleagues now show that the formins FHOD1 and INF2 localise to different podosome substructures in primary human macrophages. Using a variety of microscopy-based approaches, including a podosome reformation assay, they find that the two formins regulate different aspects of podosomes. INF2 localises to the podosome cap structure; it negatively regulates podosome size and positively affects podosomal matrix degradation. Because INF2 also regulates podosome oscillations, it most probably also plays a role in the mechanosensing ability of podosomes. FHOD1 depletion did not lead to any significant changes in overall podosome size or number, but reduced actomyosin contractility at podosome-connecting actin cables, suggesting that FHOD1 functions to regulate podosome connectivity, possibly to establish the typical regular podosome pattern at the substrate-contacting cell side. Taken together, these findings not only establish formins as new regulators of podosome function, but also highlight that these structures represent an excellent model system for the analysis of complex actin architectures in cells.
