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Modular actin nano-architecture enables podosome protrusion and mechanosensing.

Nature communications (2019-11-16)
Koen van den Dries, Leila Nahidiazar, Johan A Slotman, Marjolein B M Meddens, Elvis Pandzic, Ben Joosten, Marleen Ansems, Joost Schouwstra, Anke Meijer, Raymond Steen, Mietske Wijers, Jack Fransen, Adriaan B Houtsmuller, Paul W Wiseman, Kees Jalink, Alessandra Cambi
ABSTRACT

Basement membrane transmigration during embryonal development, tissue homeostasis and tumor invasion relies on invadosomes, a collective term for invadopodia and podosomes. An adequate structural framework for this process is still missing. Here, we reveal the modular actin nano-architecture that enables podosome protrusion and mechanosensing. The podosome protrusive core contains a central branched actin module encased by a linear actin module, each harboring specific actin interactors and actin isoforms. From the core, two actin modules radiate: ventral filaments bound by vinculin and connected to the plasma membrane and dorsal interpodosomal filaments crosslinked by myosin IIA. On stiff substrates, the actin modules mediate long-range substrate exploration, associated with degradative behavior. On compliant substrates, the vinculin-bound ventral actin filaments shorten, resulting in short-range connectivity and a focally protrusive, non-degradative state. Our findings redefine podosome nanoscale architecture and reveal a paradigm for how actin modularity drives invadosome mechanosensing in cells that breach tissue boundaries.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Vinculin antibody produced in mouse, clone hVIN-1, ascites fluid
Sigma-Aldrich
Anti-Actin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Talin antibody produced in mouse, clone 8d4, ascites fluid