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Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions
- Source :
- Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de la UB, Universidad de Barcelona, Molecular Biology of the Cell
- Publication Year :
- 2011
- Publisher :
- American Society for Cell Biology, 2011.
-
Abstract
- Cells severely depleted of filamins were observed to have numerous motility-related defects, including a defect in endoplasmic spreading; smaller, more dynamic focal adhesions; and an inability to sustain high levels of traction force. The endoplasm as a separate mechanical unit spread by pulling forces is also discussed.<br />Cell motility is an essential process that depends on a coherent, cross-linked actin cytoskeleton that physically coordinates the actions of numerous structural and signaling molecules. The actin cross-linking protein, filamin (Fln), has been implicated in the support of three-dimensional cortical actin networks capable of both maintaining cellular integrity and withstanding large forces. Although numerous studies have examined cells lacking one of the multiple Fln isoforms, compensatory mechanisms can mask novel phenotypes only observable by further Fln depletion. Indeed, shRNA-mediated knockdown of FlnA in FlnB–/– mouse embryonic fibroblasts (MEFs) causes a novel endoplasmic spreading deficiency as detected by endoplasmic reticulum markers. Microtubule (MT) extension rates are also decreased but not by peripheral actin flow, because this is also decreased in the Fln-depleted system. Additionally, Fln-depleted MEFs exhibit decreased adhesion stability that appears in increased ruffling of the cell edge, reduced adhesion size, transient traction forces, and decreased stress fibers. FlnA–/– MEFs, but not FlnB–/– MEFs, also show a moderate defect in endoplasm spreading, characterized by initial extension followed by abrupt retractions and stress fiber fracture. FlnA localizes to actin linkages surrounding the endoplasm, adhesions, and stress fibers. Thus we suggest that Flns have a major role in the maintenance of actin-based mechanical linkages that enable endoplasmic spreading and MT extension as well as sustained traction forces and mature focal adhesions.
- Subjects :
- Motilitat cel·lular
Stress fiber
Filamins
Gene Expression
macromolecular substances
Cell Communication
Cell motility
Biology
Transfection
Filamin
Microtubules
Focal adhesion
Mice
03 medical and health sciences
Contractile Proteins
0302 clinical medicine
Cell Movement
Cell Line, Tumor
Stress Fibers
Proteïnes citosquelètiques
Animals
Humans
FLNA
FLNB
Gene Silencing
RNA, Small Interfering
Cytoskeleton
Molecular Biology
Cells, Cultured
030304 developmental biology
Endoplasm
Focal Adhesions
0303 health sciences
Microfilament Proteins
Articles
Cell Biology
Fibroblasts
Actin cytoskeleton
Actins
Cell biology
Cytoskeletal proteins
Cell Motility
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de la UB, Universidad de Barcelona, Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....0909e3d719c7673aabc48c10d157fb59