HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Filla, M. S. Articles by Peters, D. M. Search for Related Content PubMed PubMed Citation Articles by Filla, M. S. Articles by Peters, D. M.

ß1 and ß3 Integrins Cooperate to Induce Syndecan-4-Containing Cross-linked Actin Networks in Human Trabecular Meshwork Cells

¹From the Department of Pathology and Laboratory Medicine, and ²Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin; and the ³Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama.

PURPOSE. To characterize the molecular composition of cross-linked actin networks (CLANs) and the regulation of their formation by integrins in normal human trabecular meshwork (TM) cells. CLANs have been observed in steroid-treated and glaucomatous TM cells and have been suggested to contribute to decreased outflow facility by altering the contractility of the TM.

METHODS. Immunofluorescence microscopy was used to identify molecular components of CLANs and quantitate CLAN formation in HTM cells plated on coverslips coated with various extracellular matrix (ECM) proteins (fibronectin, types I and IV collagen, and vitronectin), vascular cell adhesion molecule (VCAM)-1, or activating antibodies against ß1, ß3, or 2ß1 integrins. These integrin antibodies were also used as soluble ligands.

RESULTS. CLAN vertices contained the actin-binding proteins -actinin and filamin and the signaling molecules syndecan-4 and PIP₂. CLANs lacked Arp3 and cortactin. CLAN formation was dependent on the ECM substrate and was significantly higher on fibronectin and VCAM-1 compared with vitronectin, types I or IV collagen. Adsorbed ß1 integrin antibodies also induced CLANs, whereas adsorbed ß3 or 2ß1 integrin antibodies did not. Soluble ß3 integrin antibodies, however, induced CLANs and actually enhanced CLAN formation in cells spread on fibronectin, VCAM-1, type I or type IV collagen, or ß1 integrin antibodies.

CONCLUSIONS. CLANs are unique actin-branched networks whose formation can be regulated by ß1 and ß3 integrin signaling pathways. Thus, integrin-mediated signaling events can modulate the organization of the actin cytoskeleton in TM cells and hence could participate in regulating cytoskeletal events previously demonstrated to be involved in controlling outflow facility.

This article has been cited by other articles:

				K. Sanka, R. Maddala, D. L. Epstein, and P. V. Rao Influence of Actin Cytoskeletal Integrity on Matrix Metalloproteinase-2 Activation in Cultured Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2105 - 2114. [Abstract] [Full Text] [PDF]

				A. M. Malek, C. Xu, E. S. Kim, and S. L. Alper Hypertonicity triggers RhoA-dependent assembly of myosin-containing striated polygonal actin networks in endothelial cells Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1645 - C1659. [Abstract] [Full Text] [PDF]