Differential Stability of Flamingo Protein Complexes Underlies the Establishment of Planar Polarity

Abstract

SummaryBackgroundThe planar polarization of developing tissues is controlled by a conserved set of core planar polarity proteins. In the Drosophila pupal wing, these proteins adopt distinct proximal and distal localizations in apicolateral junctions that act as subcellular polarity cues to control morphological events. The core polarity protein Flamingo (Fmi) localizes to both proximal and distal cell boundaries and is known to have asymmetric activity, but the molecular basis of this asymmetric activity is unknown.ResultsWe examine the role of Fmi in controlling asymmetric localization of polarity proteins in pupal wing cells. We find that Fmi interacts preferentially with distal-complex components, rather than with proximal components, and present evidence that there are different domain requirements for Fmi to associate with distal and proximal components. We further show that distally and proximally localized proteins cooperate to allow stable accumulation of Fmi at apicolateral junctions and present evidence that the rates of endocytic trafficking of Fmi are increased when Fmi is not in a stable asymmetric complex. Finally, we provide evidence that Fmi is trafficked from junctions via both Dishevelled-dependent and Dishevelled-independent mechanisms.ConclusionsWe present a model in which the primary function of Fmi is to participate in the formation of inherently stable asymmetric junctional complexes: Removal from junctions of Fmi that is not in stable complexes, combined with directional trafficking of Frizzled and Fmi to the distal cell edge, drives the establishment of cellular asymmetry.

Wnt/PCP proteins regulate stereotyped axon branch extension inDrosophila

“…There is evidence that the extracellular regions of Stbm and Fz can physically bind to each other (Wu and Mlodzik, 2008), although this is debated (Chen et al, 2008;Lawrence et al, 2008;Strutt and Strutt, 2008). Physical associations between StbmDsh and Fz-Dsh have been documented in vertebrate and fly proteins (Park and Moon, 2002;Bastock et al, 2003;Wong et al, 2003;Torban et al, 2004;Jenny et al, 2005).…”

Evolution of GPCR: Change and continuity

“…This includes the cadherin-like family that comprises the vertebrate CELSR (Cadherin, EGF-like, LAG-like seven-pass receptor) and Drosophila flamingo/starry night receptors [38][39][40]. Members of this family are involved in the control of cell and tissue polarity and interact with wnt/frizzled signaling [41,42]. The second highly conserved class comprises members of the lectin-like (latrophilin) family named after an unusual domain related to rhamnose-binding lectins.…”

Dynamic intracellular distribution of Vangl2 during cell polarization in zebrafish gastrula

“…PCP signaling in Drosophila produces, or is a consequence of, an asymmetric distribution of some core components at the apical cell membrane (Amonlirdviman et al, 2005;Axelrod, 2001;Lawrence et al, 2004;Ma et al, 2003). Vang and Pk are enriched on one side (proximal in the wing), whereas Fz, Dsh and Dgo are enriched on the opposite side (distal in the wing) of the cell along the planar polarity axis of the tissue, with Fmi present at both cell edges (Strutt and Strutt, 2008). As a result of intercellular interactions and intracellular feedback loops, the core protein complexes have been shown to concentrate into discrete membrane subdomains or 'puncta' (Strutt et al, 2011).…”