Invadosomes - shaping actin networks to follow mechanical cues.
Invadosomes are actin-based protrusions formed by cells in response to obstacles in their microenvironment, especially basement membranes and dense interstitial matrices. A versatile set of proteins controls assembly and dynamics of the actin networks at invadosomes and adhesive molecules link them with the extracellular matrix. Furthermore, polarized delivery of proteases makes invadosomes degradative. Therefore, invadosomes have been classically viewed as specialized protrusions involved in cell migration and remodeling of the microenvironment. Recent discoveries have considerably broadened this picture by showing that invadosomes respond to traction forces and can self-organize into dynamic arrays capable of following the topography of the substrate. Although these findings suggest that invadosomes may function as mechanosensors, this possibility has not been critically evaluated. In this review, we first summarize the organization and dynamics of actin in invadosomes and their superstructures with emphasis on force-production mechanisms. Next, we outline our current understanding of how mechanical cues impinge on invadosomes and modify their behavior. From this perspective, we provide an outlook of the outstanding open questions and the main challenges in the field.
Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Katarzyna M
KM
Kedziora
Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Tadamoto
T
Isogai
Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Kees
K
Jalink
Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands, m.innocenti@nki.nl.
Metello
M
Innocenti
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001696:Biomechanical Phenomena; D060833:Cellular Microenvironment; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D000069261:Podosomes / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D000199:Actins