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 JL, Smith TC, Fang Z, Takizawa N, Luna EJ. (2009). Supervillin reorganizes the actin cytoskeleton and increases invadopodial efficiency. Open Access Articles. https://doi.org/10.1091/mbc.E08-08-0867. Retrieved from https://escholarship.umassmed.edu/oapubs/1923