Spatial control of actin organization at adherens junctions by a synaptotagmin-like protein Btsz.
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. Localization of E-cadherin is stabilized through a pathway involving the recruitment of actin filaments by E-cadherin. 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 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 apically 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.
Pilot
Fanny
F
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.
Philippe
Jean-Marc
JM
Lemmers
Céline
C
Lecuit
Thomas
T
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D050857:Synaptotagmins
D000199:Actins; D015820:Cadherins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; C400774:baz protein, Drosophila; C479933:btsz protein, Drosophila; D050857:Synaptotagmins; C071058:moesin