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© The Rockefeller University Press, 0021-9525/1999//819 $5.00
The Journal of Cell Biology, Volume 146, Number 4, , 1999 819-830

In Vivo, Villin Is Required for Ca²⁺-Dependent F-Actin Disruption in Intestinal Brush Borders

^a Institut Curie, UMR 144, 75248 Paris, France
^b Unité de Biologie du Développement, Centre National de la Recherche Scientifique, URA 1960, Institut Pasteur, 75015 Paris, France
^c Ecole Nationale Vétérinaire d'Alfort, 94700 Maisons-Alfort, France
UMR 144, Laboratoire de Morphogénèse et Signalisation Cellulaires, Institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France.33-1-42-34-63-7733-1-42-34-63-62

Sylvie.Robine{at}curie.fr

Villin is an actin-binding protein localized in intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a Ca²⁺-dependent manner. We generated knockout mice to study the role of villin in vivo. In villin-null mice, no noticeable changes were observed in the ultrastructure of the microvilli or in the localization and expression of the actin-binding and membrane proteins of the intestine. Interestingly, the response to elevated intracellular Ca²⁺ differed significantly between mutant and normal mice. In wild-type animals, isolated brush borders were disrupted by the addition of Ca²⁺, whereas Ca²⁺ had no effect in villin-null isolates. Moreover, increase in intracellular Ca²⁺ by serosal carbachol or mucosal Ca²⁺ ionophore A23187 application abolished the F-actin labeling only in the brush border of wild-type animals. This F-actin disruption was also observed in physiological fasting/refeeding experiments. Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 ± 9.6%, compared with wild-type mice, 70 ± 8.8%, at day 13. These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals. We postulate that this property might be involved in cellular plasticity related to cell injury.

Key Words: villin knockout • intestine • actin-binding proteins • microvilli • mouse

© 1999 The Rockefeller University Press

F. Jaisser and S. Robine contributed equally to this paper. This work has been presented in part at the 6th International Congress on Cell Biology in San Francisco on 7–11 December 1996. Portions of this work have appeared in abstract form (1996. Mol. Biol. Cell. 7[Suppl.]:2a and 542a).

E. Ferrary's present address is Institut Nationale de la Santé et Recherche Médicale, U426, Faculté Xavier Bichat, 75018 Paris, France.

F. Jaisser's present address is Institut Nationale de la Santé et Recherche Médicale, U428, Faculté Xavier Bichat, 75018 Paris, France.

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This article has been cited by other articles:

• DeRosier, D. J., Tilney, L. G. (2000). F-Actin Bundles Are Derivatives of Microvilli: What Does This Tell US about How Bundles Might Form?. JCB 148: 1-6 [Full Text]  

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