RT Journal Article
SR Electronic
T1 Modular actin nano-architecture enables podosome protrusion and mechanosensing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 583492
DO 10.1101/583492
A1 Koen van den Dries
A1 Leila Nahidiazar
A1 Johan A. Slotman
A1 Marjolein B.M. Meddens
A1 Elvis Pandzic
A1 Ben Joosten
A1 Marleen Ansems
A1 Joost Schouwstra
A1 Anke Meijer
A1 Raymond Steen
A1 Mietske Wijers
A1 Jack Fransen
A1 Adriaan B. Houtsmuller
A1 Paul W. Wiseman
A1 Kees Jalink
A1 Alessandra cambi
YR 2019
UL http://biorxiv.org/content/early/2019/03/20/583492.abstract
AB 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.