Small GTPases all over invadosomes

Abstract

Cell invasion is associated with numerous patho-physiologic states including cell development and metastatic dissemination. This process couples the activation of cell motility with the capacity to degrade the extracellular matrix, thereby permitting cells to pass through basal membranes. Invasion is sustained by the actions of invadosomes, an ensemble of subcellular structures with high functional homology. Invadosomes are 3D acto-adhesive structures that can also mediate local extracellular matrix degradation through the controlled delivery of proteases. Intracellular RHO GTPases play a central role in the regulation of invadosomes where their complex interplay regulates multiple invadosome functions. This review aims to provide an overview of the synergistic activities of the small GTPases in invadosome biology. This broad-based review also reinforces the importance of the spatiotemporal regulation of small GTPases and the impact of this process on invadosome dynamics.

Keywords: Small GTPase; invadopodia; invadosomes; linear invadosomes; podosomes; spatiotemporal signalling.

Figure 1.

Scheme depicting the actions of various small GTPases and their regulators (GEFs, GAPs, and GDIs) and their role in promoting invadosome formation as well as coupling of its acto-adhesive and ECM degradative activities