Department of Cell Biology
Actins; Animals; Biological Markers; COS Cells; Cattle; Cell Line, Tumor; Cercopithecus aethiops; Cortactin; Cytoskeleton; Extracellular Matrix; Focal Adhesions; Green Fluorescent Proteins; Humans; Membrane Proteins; Microfilament Proteins; Protein Binding; Protein Transport; Pseudopodia; Recombinant Fusion Proteins; src-Family Kinases
Cell Biology | Life Sciences | Medicine and Health Sciences
Tumor cells use actin-rich protrusions called invadopodia to degrade extracellular matrix (ECM) and invade tissues; related structures, termed podosomes, are sites of dynamic ECM interaction. We show here that supervillin (SV), a peripheral membrane protein that binds F-actin and myosin II, reorganizes the actin cytoskeleton and potentiates invadopodial function. Overexpressed SV induces redistribution of lamellipodial cortactin and lamellipodin/RAPH1/PREL1 away from the cell periphery to internal sites and concomitantly increases the numbers of F-actin punctae. Most punctae are highly dynamic and colocalize with the podosome/invadopodial proteins, cortactin, Tks5, and cdc42. Cortactin binds SV sequences in vitro and contributes to the formation of enhanced green fluorescent protein (EGFP)-SV induced punctae. SV localizes to the cores of Src-generated podosomes in COS-7 cells and with invadopodia in MDA-MB-231 cells. EGFP-SV overexpression increases average numbers of ECM holes per cell; RNA interference-mediated knockdown of SV decreases these numbers. Although SV knockdown alone has no effect, simultaneous down-regulation of SV and the closely related protein gelsolin reduces invasion through ECM. Together, our results show that SV is a component of podosomes and invadopodia and that SV plays a role in invadopodial function, perhaps as a mediator of cortactin localization, activation state, and/or dynamics of metalloproteinases at the ventral cell surface.
DOI of Published Version
Mol Biol Cell. 2009 Feb;20(3):948-62. Epub 2008 Dec 24. Link to article on publisher's site
Molecular biology of the cell
Crowley, Jessica Lynn; Smith, Tara C.; Fang, Zhiyou; Takizawa, Norio; and Luna, Elizabeth J., "Supervillin reorganizes the actin cytoskeleton and increases invadopodial efficiency" (2009). Open Access Articles. 1923.