1. Institut de Biologie du Développement de Marseille Luminy (IBDML) UMR 6216, CNRS-Université de la Méditerrannée. Campus de Luminy, case 907, 13288 Marseille cedex 09, France

Correspondence to: Thomas Lecuit¹ Correspondence and requests for materials should be addressed to T.L. (Email: lecuit@ibdm.univ-mrs.fr).

Abstract

Epithelial tissues maintain a robust architecture during development. This fundamental property relies on intercellular adhesion through the formation of adherens junctions containing E-cadherin molecules^{1, 2}. Localization of E-cadherin is stabilized through a pathway involving the recruitment of actin filaments by E-cadherin^{3, 4, 5, 6}. Here we identify an additional pathway that organizes actin filaments in the apical junctional region (AJR) where adherens junctions form in embryonic epithelia. This pathway is controlled by Bitesize (Btsz), a synaptotagmin-like protein^{7, 8} that is recruited in the AJR independently of E-cadherin and is required for epithelial stability in Drosophila embryos. On loss of btsz, E-cadherin is recruited normally to the AJR, but is not stabilized properly and actin filaments fail to form a stable continuous network. In the absence of E-cadherin, actin filaments are stable for a longer time than they are in btsz mutants. We identify two polarized cues that localize Btsz: phosphatidylinositol (4,5)-bisphosphate, to which Btsz binds; and Par-3. We show that Btsz binds to the Ezrin–Radixin–Moesin protein Moesin, an F-actin-binding protein that is localized apically⁹ and is recruited in the AJR in a btsz-dependent manner. Expression of a dominant-negative form of Ezrin that does not bind F-actin phenocopies the loss of btsz. Thus, our data indicate that, through their interaction, Btsz and Moesin may mediate the proper organization of actin in a local domain, which in turn stabilizes E-cadherin. These results provide a mechanism for the spatial order of actin organization underlying junction stabilization in primary embryonic epithelia.

1. Institut de Biologie du Développement de Marseille Luminy (IBDML) UMR 6216, CNRS-Université de la Méditerrannée. Campus de Luminy, case 907, 13288 Marseille cedex 09, France

Correspondence to: Thomas Lecuit¹ Correspondence and requests for materials should be addressed to T.L. (Email: lecuit@ibdm.univ-mrs.fr).

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