Details

Autor(en) / Beteiligte

• van den Dries, Koen
• Nahidiazar, Leila
• Slotman, Johan A.
• Meddens, Marjolein B. M.
• Pandzic, Elvis
• Joosten, Ben
• Ansems, Marleen
• Schouwstra, Joost
• Meijer, Anke
• Steen, Raymond
• Wijers, Mietske
• Fransen, Jack
• Houtsmuller, Adriaan B.
• Wiseman, Paul W.
• Jalink, Kees
• Cambi, Alessandra

Titel

Modular actin nano-architecture enables podosome protrusion and mechanosensing

Ist Teil von

• Nature communications, 2019-11, Vol.10 (1), p.5171-16, Article 5171

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Podosomes are actin-based protrusions used by cells for invasion and local degradation but the structure underlying their protrusiveness and mechanosensitivity is unclear. Here, the authors report that podosomes have a modular actin nano-architecture whose organization differs on stiff or soft substrates.