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Research Database PMU-SQQUID

Actin cytoskeleton remodelling via local inhibition of contractility at discrete microdomains.
Burgstaller, G; Gimona, M;
J Cell Sci. 2004; 117(Pt 2): 22-31.
Originalarbeiten (Zeitschrift)

PMU-Authors

Gimona Mario

Abstract

Activation of conventional protein kinase C by phorbol ester triggers the Src-dependent remodelling of the actin cytoskeleton and the formation of podosomes in vascular smooth muscle cells. Rearrangement of actin cytoskeleton in response to phorbol-12,13-dibutyrate is characterised by the simultaneous disassembly of peripheral actin stress fibres and focal adhesions, focal de novo actin polymerisation and actomyosin contraction in the cell center, indicating a spatially and temporally segregated, differential modulation of actin-cytoskeleton stability and turnover. Taking advantage of the prominent actin cytoskeleton in A7r5 cells we show here, that the molecular basis for the local inhibition of contractility is the specific recruitment of p190RhoGAP to specialised. microdomains at the focal adhesion/stress fibre interface, which are constitutively enriched in cortactin. The microdomains contain structurally altered actin filaments inaccessible to phalloidin. However, the filaments remain decorated with high molecular weight tropomyosins. Clustering of cortactin during podosome formation causes the rapid, local dispersion of myosin and tropomyosin, and interferes with the F-actin binding of h1calponin, consistent with a RhoGAP-mediated reduction of contractility. Phorbol ester-induced podosome formation is efficiently blocked by expression of constitutively active Dia1, which leads to the dispersion of cortactin. The results provide direct evidence for the spatially restricted inhibition of contractility via the recruitment and accumulation of cortactin and p190RhoGAP.


Useful keywords (using NLM MeSH Indexing)

Actins/metabolism*

Animals

Calcium-Binding Proteins/metabolism

Cells, Cultured

Cloning, Molecular

Cortactin

Cytoskeleton/metabolism*

DNA-Binding Proteins

Focal Adhesions/metabolism

Guanine Nucleotide Exchange Factors/metabolism

Microfilament Proteins/metabolism*

Microscopy, Fluorescence

Myocytes, Smooth Muscle/metabolism

Nuclear Proteins/metabolism

Phalloidine/pharmacology

Phorbol 12,13-Dibutyrate/pharmacology

Protein Kinase C/drug effects

Protein Kinase C/metabolism

Protozoan Proteins/metabolism

Rats

Repressor Proteins

Stress Fibers/metabolism*

Tropomyosin/metabolism


Find related publications in this database (Keywords)

p190RhoGAP
smooth muscle
myosin
cortactin
podosomes