Podosomes: Multipurpose organelles?

•Podosomes are sites of adhesion, mechanosensing and matrix degradation or membrane fusion.•Podosomes are single functional entities but function in groups at the cellular level.•Podosome construction, distribution and function are based on actin dynamics.•Podosome formation and organization are dictated by the microenvironment.•Podosome biogenesis is altered in some genetic diseases and podosome equivalents are assembled by cancer cells.

Thirty years of research have accumulated ample evidence that podosome clusters qualify as genuine cellular organelles that are being found in more and more cell types. A podosome is a dynamic actin-based and membrane-bound microdomain and the organelle consists in an interconnected network of such basic units, forming a cytoskeletal superstructure linked to the plasma membrane. At this strategic location, podosomes are privileged sites of interactions with the pericellular environment that regulates their formation, density, lifetime, distribution, architecture and functioning. Actin polymerization is the driving force behind most podosome characteristics. In contrast to classical organelles, podosomes are not vital at the cell level but rather serve diverse and often intricate functions of which adhesion, matrix degradation and substrate sensing are the most established. These capabilities involve specific molecules, depend on podosome organization and may vary according to the cell type in which they form. Podosome-associated diseases manifest by loss or gain of podosome functions and include genetic diseases affecting podosome components and various cancers where tumor cells ectopically express podosome equivalents (invadopodia).