QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 29 January 2003
doi: 10.1242/jcs.00322

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00322v1 116/6/1001    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Baumgartner, W. Articles by Drenckhahn, D. Search for Related Content PubMed PubMed Citation Articles by Baumgartner, W. Articles by Drenckhahn, D.

Cadherin function probed by laser tweezer and single molecule fluorescence in vascular endothelial cells

¹ Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstr. 6, D-97070 Würzburg, Germany
² Institute of Biophysics, University of Linz, Altenbergerstr. 69, A-4040 Linz, Austria

^* Author for correspondence (e-mail: anat015{at}mail.uni-wuerzburg.de)

Accepted 13 December 2002

In endothelial monolayers agonist-induced influx of Ca²⁺ and activities of the actin cytoskeleton have been shown to be crucially involved in regulation of barrier properties. By laser tweezer application we demonstrated that the strength of adhesion of VE-cadherin-coated microspheres to the surface of cultured endothelial monolayers is significantly reduced by treatment with two well-established permeability-increasing compounds, cytochalasin D and the Ca²⁺-ionophore A23187, which shows that both compounds directly affect cadherin-mediated adhesion. Cytochalasin D and A23187 caused considerable decay of F-actin (30-60%). Stabilisation of F-actin by jasplakinolide completely blocked drug-induced weakening of bead adhesion showing that attenuation of cadherin-cadherin trans-interaction induced by cytochalasin D and A23187 depends largely on downregulation of F-actin. Single molecule fluorescence microscopy demonstrated that drug-induced weakening of adhesion is accompanied by an increase in lateral mobility of cadherins as well as by dispersal of cadherin-enriched plasmalemmal microdomains. However, the lifetime (700 milliseconds, k_off1.4 second^–1) and apparent on-rate of cadherin trans-interaction (relative frequency of binding) remained unchanged in response to cytochalasin D and A23187 indicating that cadherin-mediated adhesion is not modulated by inside-out changes of the affinity but, rather, appears to be controlled by actin-dependent tethering and compartmentalization of cadherins.

Key words: VE-cadherin, Biophysics, Permeability, Actin

This article has been cited by other articles:

				K. Muller-Marschhausen, J. Waschke, and D. Drenckhahn Physiological hydrostatic pressure protects endothelial monolayer integrity Am J Physiol Cell Physiol, January 1, 2008; 294(1): C324 - C332. [Abstract] [Full Text] [PDF]

				N. Schlegel, S. Burger, N. Golenhofen, U. Walter, D. Drenckhahn, and J. Waschke The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier stabilization Am J Physiol Cell Physiol, January 1, 2008; 294(1): C178 - C188. [Abstract] [Full Text] [PDF]

				L. Carramusa, C. Ballestrem, Y. Zilberman, and A. D. Bershadsky Mammalian diaphanous-related formin Dia1 controls the organization of E-cadherin-mediated cell-cell junctions J. Cell Sci., November 1, 2007; 120(21): 3870 - 3882. [Abstract] [Full Text] [PDF]

				L. A. Chtcheglova, J. Waschke, L. Wildling, D. Drenckhahn, and P. Hinterdorfer Nano-Scale Dynamic Recognition Imaging on Vascular Endothelial Cells Biophys. J., July 15, 2007; 93(2): L11 - L13. [Abstract] [Full Text] [PDF]

				O. Thoumine, M. Lambert, R.-M. Mege, and D. Choquet Regulation of N-Cadherin Dynamics at Neuronal Contacts by Ligand Binding and Cytoskeletal Coupling Mol. Biol. Cell, February 1, 2006; 17(2): 862 - 875. [Abstract] [Full Text] [PDF]

				P. Panorchan, M. S. Thompson, K. J. Davis, Y. Tseng, K. Konstantopoulos, and D. Wirtz Single-molecule analysis of cadherin-mediated cell-cell adhesion J. Cell Sci., January 1, 2006; 119(1): 66 - 74. [Abstract] [Full Text] [PDF]

				J. Waschke, F. E. Curry, R. H. Adamson, and D. Drenckhahn Regulation of actin dynamics is critical for endothelial barrier functions Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1296 - H1305. [Abstract] [Full Text] [PDF]

				J. Waschke, D. Drenckhahn, R. H. Adamson, and F. E. Curry Role of adhesion and contraction in Rac 1-regulated endothelial barrier function in vivo and in vitro Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H704 - H711. [Abstract] [Full Text] [PDF]

				H. Delanoe-Ayari, R. Al Kurdi, M. Vallade, D. Gulino-Debrac, and D. Riveline Membrane and acto-myosin tension promote clustering of adhesion proteins PNAS, February 24, 2004; 101(8): 2229 - 2234. [Abstract] [Full Text] [PDF]

				J. Waschke, W. Baumgartner, R. H. Adamson, M. Zeng, K. Aktories, H. Barth, C. Wilde, F. E. Curry, and D. Drenckhahn Requirement of Rac activity for maintenance of capillary endothelial barrier properties Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H394 - H401. [Abstract] [Full Text] [PDF]

				A. Minagar and J S. Alexander Blood-brain barrier disruption in multiple sclerosis Multiple Sclerosis, December 1, 2003; 9(6): 540 - 549. [Abstract] [PDF]