Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway

Patrik K.M. Asp, Margareta Wihlborg, Mattias Karlén, Ann Kristin Östlund Farrants

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The human BRG1 (brahma-related gene 1) protein is a component of the SWI/SNF family of the ATP-dependent chromatin remodelling complexes. We show here that expression of the BRG1 protein, but not of an ATPase-deficient BRG1 protein, in BRG1-deficient SW13 cells alters the organisation of actin filaments. BRG1 expression induces the formation of thick actin filament bundles resembling stress-fibres, structures that are rarely seen in native SW13 cells. BRG1 expression does not influence the activity state of the RhoA-GTPase, which is involved in stress-fibre formation. We find that RhoA is equally activated by stimuli, such as serum, in BRG1-expressing cells, ATPase-deficient BRG1-expressing cells and native SW13 cells. However, the activation of RhoA by lysophosphatidic acid and serum does not trigger the formation of stress-fibre-like structures in SW13 cells. Activation of the RhoA-GTPase in BRG1-expressing cells induces stress-fibre-like structures, indicating that the BRG1 can couple RhoA activation to stress-fibre formation. At least two downstream effectors are involved in stress-fibre formation, Rho-kinase/ROCK and Dia. BRG1 expression, but not the expression of the ATP-deficient BRG1, increases the protein level of ROCK1, one form of the Rho-kinase/ROCK. That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation. No specificity between the two Rho-kinase/ROCK forms exists. Our results suggest that the BRG1 protein affects the RhoA pathway by increasing the protein level of ROCK1, which allows stress-fibre-like structures to form.

Original languageEnglish (US)
Pages (from-to)2735-2746
Number of pages12
JournalJournal of Cell Science
Volume115
Issue number13
StatePublished - Jul 1 2002
Externally publishedYes

Fingerprint

Stress Fibers
Actin Cytoskeleton
rho-Associated Kinases
Genes
GTP Phosphohydrolases
Proteins
Gene Expression
Adenosine Triphosphatases
Adenosine Triphosphate
Chromatin Assembly and Disassembly
Serum

Keywords

  • Actin filament organisation
  • BRG1
  • Rho kinases
  • RhoA
  • SWI/SNF

ASJC Scopus subject areas

  • Cell Biology

Cite this

Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway. / Asp, Patrik K.M.; Wihlborg, Margareta; Karlén, Mattias; Östlund Farrants, Ann Kristin.

In: Journal of Cell Science, Vol. 115, No. 13, 01.07.2002, p. 2735-2746.

Research output: Contribution to journalArticle

Asp, Patrik K.M. ; Wihlborg, Margareta ; Karlén, Mattias ; Östlund Farrants, Ann Kristin. / Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway. In: Journal of Cell Science. 2002 ; Vol. 115, No. 13. pp. 2735-2746.
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AB - The human BRG1 (brahma-related gene 1) protein is a component of the SWI/SNF family of the ATP-dependent chromatin remodelling complexes. We show here that expression of the BRG1 protein, but not of an ATPase-deficient BRG1 protein, in BRG1-deficient SW13 cells alters the organisation of actin filaments. BRG1 expression induces the formation of thick actin filament bundles resembling stress-fibres, structures that are rarely seen in native SW13 cells. BRG1 expression does not influence the activity state of the RhoA-GTPase, which is involved in stress-fibre formation. We find that RhoA is equally activated by stimuli, such as serum, in BRG1-expressing cells, ATPase-deficient BRG1-expressing cells and native SW13 cells. However, the activation of RhoA by lysophosphatidic acid and serum does not trigger the formation of stress-fibre-like structures in SW13 cells. Activation of the RhoA-GTPase in BRG1-expressing cells induces stress-fibre-like structures, indicating that the BRG1 can couple RhoA activation to stress-fibre formation. At least two downstream effectors are involved in stress-fibre formation, Rho-kinase/ROCK and Dia. BRG1 expression, but not the expression of the ATP-deficient BRG1, increases the protein level of ROCK1, one form of the Rho-kinase/ROCK. That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation. No specificity between the two Rho-kinase/ROCK forms exists. Our results suggest that the BRG1 protein affects the RhoA pathway by increasing the protein level of ROCK1, which allows stress-fibre-like structures to form.

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