Interactions between Drosophila IgCAM adhesion receptors and cindr, the Cd2ap/Cin85 ortholog

Background: Morphogenetic modeling of tissues requires coordinated regulation of adhesion. For its correct patterning, the Drosophila pupal eye requires several Immunoglobulin superfamily cell adhesion molecules (IgCAMs) and the adaptor protein Cindr. Orthologs of these proteins are essential components of specialized junctions of the vertebrate kidney; the Cindr ortholog Cd2ap is essential for the integrity of this structure. Results: Reducing Cindr during fly eye development led to incorrect distribution of the IgCAMs Roughest (Rst) and Hibris (Hbs). Both bound Cindr. Disrupting endocytosis similarly led to Rst and Hbs mis‐localization; our data suggests an additional early requirement for endocytosis in regulating Hbs localization or stability. Finally, Rst and Hbs localized correctly only when in stable membrane complexes and we propose that Cindr anchors these to the cytoskeleton. This regulation likely does not extend to IgCAMs Kin of irre (Kirre) and Sticks and stones (Sns) in the pupal eye; neither interacted with Cindr in in vitro assays. Nonetheless, Kirre and Sns partially mis‐localized when Cindr was reduced, possibly due to interactions with Rst/Hbs. Conclusions: Our data suggests Cindr recapitulates both proposed functions of its mammalian orthologs Cd2ap and Cin85: targeting the IgCAMs Rst and Hbs for endocytosis and stabilizing these heterophilic IgCAM complexes. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.

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