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PMID: 9285815 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction.

Molecular biology of the cell ·Vol. 8 ·No. 8 ·1997-08-00 ·Pages 1415-25

Zhang Q, Magnusson MK, Mosher DF

Abstract

Fibronectin (FN) matrix assembly is a cell-dependent process mediated by cell surface-binding sites for the 70-kDa amino-terminal region of FN. We have shown recently that lysophosphatidic acid (LPA) is a stimulator of FN matrix assembly. Disruption of microtubules has been shown to mimic some of the intracellular effects of LPA including the formation of actin stress fibers and myosin light chain phosphorylation. We compared the effects of microtubule disruption and LPA on FN binding and actin cytoskeleton organization. The disruption of microtubules by nocodazole or vinblastine increased FN binding to adherent cells. The modulation of binding sites was rapid, dynamic, and reversible. Enhanced binding was due to increases in both the number and affinity of binding sites. These effects are similar to the effects of LPA on FN binding. Binding induced by nocodazole was inhibited by the microtubule-stabilizing agent Taxol but not by pretreatment with a concentration of phospholipase B that totally abolished the stimulatory effect of LPA. Fluorescence microscopy revealed a close correlation among actin stress fiber formation, cell contraction, and FN binding. Blockage of the small GTP binding protein Rho or actin-myosin interactions inhibited the effects of both nocodazole and LPA on FN binding. These observations demonstrate that Rho-dependent actin stress fiber formation and cell contraction induce increased FN binding and represent a rapid labile way that cells can modulate FN matrix assembly.

MeSH Terms
Animals Antineoplastic Agents/pharmacology Antineoplastic Agents, Phytogenic/pharmacology Cattle Cytoskeleton/drug effects Endothelium/drug effects,metabolism Fibronectins/metabolism Humans Lysophospholipids/pharmacology Microfilament Proteins/metabolism Microtubules/drug effects,metabolism Nocodazole/pharmacology Osteosarcoma Paclitaxel/pharmacology Tumor Cells, Cultured Vinblastine/pharmacology
Chemicals
Antineoplastic Agents Antineoplastic Agents, Phytogenic Fibronectins Lysophospholipids Microfilament Proteins Vinblastine Paclitaxel Nocodazole
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhang Q
Department of Medicine, University of Wisconsin-Madison 53706, USA.
Magnusson M K
Mosher D F
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
1997-08-00
Pages
1415-25
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC276166
Subset
IM
Grants
NHLBI NIH HHS · HL-21644 · United States
Analysis Services
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