UMMS Affiliation

Department of Cell Biology

Publication Date

2009-02-26

Document Type

Article

Subjects

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

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

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

10.1091/mbc.E08-08-0867

Source

Mol Biol Cell. 2009 Feb;20(3):948-62. Epub 2008 Dec 24. Link to article on publisher's site

Journal/Book/Conference Title

Molecular biology of the cell

Related Resources

Link to Article in PubMed

PubMed ID

19109420

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