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J. Biol. Chem., Vol. 278, Issue 48, 47707-47712, November 28, 2003

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Different Molecular Motors Mediate Platelet-derived Growth Factor and Lysophosphatidic Acid-stimulated Floating Collagen Matrix Contraction^*

Masatoshi Abe, Chin-Han Ho, Kristine E. Kamm¶, and Frederick Grinnell||

From the Departments of Cell Biology and ^¶Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039

Fibroblast-collagen matrix contraction has been used as a model system to study how cells organize connective tissue. Previous work showed that lysophosphatidic acid (LPA)-stimulated floating collagen matrix contraction is independent of Rho kinase, whereas platelet-derived growth factor (PDGF)-stimulated contraction is Rho kinase-dependent. The current studies were carried out to learn more about the molecular motors responsible for LPA- and PDGF-stimulated contraction. We found that neither PDGF nor LPA-dependent contractile mechanisms require myosin II regulatory light chain kinase or increased phosphorylation of myosin II regulatory light chain (measured as diphosphorylation). Low concentrations of the specific myosin II inhibitor blebbistatin blocked PDGF-stimulated matrix contraction and LPA-stimulated retraction of fibroblast dendritic extensions but not LPA-stimulated matrix contraction. These data suggest that PDGF- and LPA-stimulated floating matrix contraction utilize myosin II-dependent and -independent mechanisms, respectively. LPA-dependent, Rho kinase-independent force generation also was detected during fibroblast spreading on collagen-coated coverslips.

Received for publication, June 12, 2003 , and in revised form, August 11, 2003.

^* This work was supported by NIGMS Grant GM31321 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Dermatology, Gunma University Graduate School of Medicine, Japan.

^|| To whom correspondence should be addressed: Dept. of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039. Tel.: 214-648-2181; Fax: 214-648-8694, E-mail: frederick.grinnell{at}utsouthwestern.edu.

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