UMMS Affiliation

Department of Cell Biology; Department of Physiology; Program in Molecular Medicine

Date

8-2-2006

Document Type

Article

Subjects

Adaptor Proteins, Signal Transducing; Animals; COS Cells; Cattle; Cells, Cultured; Cercopithecus aethiops; Down-Regulation; Focal Adhesions; Green Fluorescent Proteins; Humans; Membrane Proteins; Mice; Microfilament Proteins; Microtubule-Associated Proteins; Myocytes, Smooth Muscle; Nuclear Proteins; Protein Binding; Rats; Regulatory Sequences, Nucleic Acid; Transcription Factors

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

Cell-substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)--a peripheral membrane protein that binds myosin II and F-actin in such cells--negatively regulates stress fibers, FAs, and cell-substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor-interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs. Thus, SV interactions with TRIP6 at FAs promote loss of FA structure and function. SV and TRIP6 binding partners suggest several specific mechanisms through which the SV-TRIP6 interaction may regulate FA maturation and/or disassembly.

Rights and Permissions

Citation: J Cell Biol. 2006 Jul 31;174(3):447-58. Link to article on publisher's site

Related Resources

Link to article in PubMed

PubMed ID

16880273

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