PtdIns(3,4)P2 instigates focal adhesions to generate podosomes

Abstract

Cell-to-extracellular matrix (ECM) adhesion plays important roles in various biological events, such as proliferation, differentiation and migration. Distinct from other types of adhesion structures (focal complexes, focal adhesions and so on), podosomes and invadopodia are thought to have additional functions beyond attachment, possibly including invasion into the ECM. for podosomes and invadopodia to invade into the ECM, molecules involved in adhesion, actin polymerization and ECM degradation must be recruited to sites of action. Our recent study demonstrated that podosomes form near newly formed focal adhesions via the minimally expressed phosphoinositide PtdIns(3,4) P2-mediated recruitment of the Tks5-Grb2 scaffold, followed by the accumulation of N-WASP. Although this study demonstrated details of molecular interplay during the transformation of focal adhesion, its regulation in the in vivo invasion process remains to be clarified. Here, we discuss the molecular bases of the transformation of focal adhesions to podosomes/invadopodia based on current understanding.

Figure 1

NIH-src cells in Matrigel form protrusions enriched with N-WASP and F-actin. NIH-src cells cultured in Matrigel (BD bioscience) were fixed with 2% paraformaldehyde in phosphate buffered saline for 10 min. Cells were then stained with anti-integrinβ1 (Chemicon, MAB1997) (red), anti-N-WASP (green) and Alexa647-phalloidin (Invitrogen) to visualize F-actin (blue). Arrowheads indicate protrusions with N-WASP and F-actin accumulation. The confocal images were sequentially taken between 16.52 µm and 41.46 µm from the glass surface; therefore, the image represents a 29.42 µm section (Olympus, FV1000 confocal microscopy system with 40x objective, NA 0.60). Scale bar, 20 µm.