The actin organization that is responsible for the formation of an adherens junction — which, in turn, connects the actin cytoskeletons of two neighbouring cells — is mediated partly by Bitesize (Btsz). Reporting this finding in Nature, Pilot et al. explore the knockdown and binding partners of Btsz in Drosophila melanogaster embryos.
Using a microarray screen for genes that are involved in epithelial morphogenesis, Pilot et al. initially identified btsz, which encodes a synaptotagmin-like protein, as being involved in epithelial integrity. Following the knockdown of btsz, adherens junctions still formed and a crucial organizational protein, E-cadherin, was still recruited to the junctions. But, these junctions appeared fragmented under the microscope, were unstable, and led to a rapid collapse of the epithelial structure. A time-lapse analysis of the Btsz-deficient adherens junctions showed that E-cadherin localization along the adherens junctions was initially normal — that is, homogeneous — but subsequently became heterogeneous. These findings, therefore, indicate that Btsz is involved in the stabilization of E-cadherin rather than its localization.
Additional microscopy studies showed that the actin cytoskeleton was disorganized along adherens junctions as a result of btsz knockdown. E-cadherin knockdown, however, had less affect on the actin cytoskeleton. As these results indicate that Btsz affects the actin cytoskeleton through an E-cadherin-independent pathway, the researchers further examined the relationship between Btsz and actin. Btsz was shown to bind to Moesin — a protein that also binds filamentous actin — and to colocalize with Moesin and E-cadherin at the sites of adherens junctions in wild-type D. melanogaster embryos. But in btsz-knockdown or btsz-mutant embryos, Moesin localization to the necessary sites was diminished. Furthermore, the overexpression of a Moesin-orthologue mutant that lacked the actin-binding domain of Moesin resulted in defects that were similar to btsz-mutant embryos.
The authors' findings show that Btsz binds and localizes Moesin, and thereby affects actin cytoskeleton rearrangement, resulting in the stabilization of E-cadherin molecules, adherens junctions and epithelial organization. But, these Btsz findings leave us hungry for more. Particularly, do the seven mammalian orthologues of Btsz have a similar function in actin organization? And, as synaptotagmin-like proteins have also been linked to vesicle trafficking, is this process implicated in adherens-junction formation?