Echinoid regulates Flamingo endocytosis to control ommatidial rotation in theDrosophilaeye

Abstract

SUMMARYPlanar cell polarity (PCP) refers to a second polarity axis orthogonal to the apicobasal axis in the plane of the epithelium. The molecular link between apicobasal polarity and PCP is largely unknown. During Drosophila eye development, differentiated photoreceptors form clusters that rotate independently of the surrounding interommatidial cells (ICs). Here, we demonstrate that both Echinoid (Ed), an adherens junction-associated cell adhesion molecule, and Flamingo (Fmi), a PCP determinant, are endocytosed via a clathrin-mediated pathway in ICs. Interestingly, we found that Ed binds the AP-2 adaptor and is required for the internalization of Fmi into ICs. Loss of ed led to increased amounts of Fmi on the cell membrane of non-rotating ICs and also to the misrotation of photoreceptor clusters. Importantly, overexpression of fmi in ICs alone was sufficient to cause misrotation of the adjacent photoreceptor clusters. Together, we propose that Ed, when internalized by AP-2, undergoes co-endocytosis with, and thereby decreases, Fmi levels on non-rotating ICs to permit correct rotation of ommatidial clusters. Thus, co-endocytosis of Ed and Fmi provides a link between apicobasal polarity and PCP.

Novel transport function of adherens junction revealed by live imaging in Drosophila

“…We previously showed that in the interommatidial cells of the eye disc, Ed is endocytosed via an AP-2-, dynamin-and Rab5-dependent pathway [15], and we confirmed this in the lateral epithelial cells (Fig. S3 B-D).…”

“…Thus, Ed might engage in non-cellautonomous processes. Consistent with this, we previously demonstrated that ed acts non-autonomously to generate extra R7 photoreceptor cells and to promote ommatidial rotation during eye development [15,21]. Finally, many signaling receptors remain active in the endosomes following receptor-mediated endocytosis [22].…”

Mink1 Regulates β-Catenin-Independent Wnt Signaling via Prickle Phosphorylation

“…For instance, Frizzled and Fmi have been observed in rapidly moving intracellular vesicles undergoing polarized transport on microtubules, and the functional inhibition of endosomal trafficking was shown to alter their asymmetrical localization in flies (42,46). Interestingly, the regulation of Fmi traffic into clathrin-coated vesicles by the membrane protein Echinoid was shown to be essential for ommatidial PCP (22). Adding to this mechanism, Rab5 was implicated for the endocytic trafficking and apical localization of Fmi and the establishment of PCP in the Drosophila wing (32), as well as for the localization of E-cadherin during zebrafish gastrulation (52).…”

Planar Cell Polarity Signaling in the Drosophila Eye

“…Indeed, two additional cell adhesion molecules, the IgCAM Echinoid (Ed), capable of homophilic and heterophilic interactions (Islam et al ., 2003), as well as its paralog Fred (Friend of Echinoid), have recently been described to be required for proper rotation (Fetting et al ., 2009; Ho et al ., 2010). While loss of their function causes a wide variation in the rotation angle of individual ommatidia, genetic interactions showed that ed and fred antagonistically interact with the EGFR signaling components pointed and canoe (Fetting et al ., 2009).…”

“…In contrast, fred mutations suppress loss of cno or pnt , again pointing toward a tight interplay between EGFR signaling, cell adhesion, and rotation. Interestingly, Ed appears to be enriched in cells newly recruited into the PR clusters and the neighboring IOCs, but reduced in the rotating preclusters and their contact interfaces with IOCs (Fetting et al ., 2009; Ho et al ., 2010; Fig. 7.5B).…”