Flamingo, a Seven-Pass Transmembrane Cadherin, Regulates Planar Cell Polarity under the Control of Frizzled

Abstract

We identified a seven-pass transmembrane receptor of the cadherin superfamily, designated Flamingo (Fmi), localized at cell-cell boundaries in the Drosophila wing. In the absence of Fmi, planar polarity was distorted. Before morphological polarization of wing cells along the proximal-distal (P-D) axis, Fmi was redistributed predominantly to proximal and distal cell edges. This biased localization of Fmi appears to be driven by an imbalance of the activity of Frizzled (Fz) across the proximal/distal cell boundary. These results, together with phenotypes caused by ectopic expression of fz and fmi, suggest that cells acquire the P-D polarity by way of the Fz-dependent boundary localization of Fmi.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…The 'PCP' core components include several transmembrane proteins, such as Frizzled (Fz) (Adler et al, 1997;Vinson and Adler, 1987), Strabismus (Stbm)/Van Gogh (Vang) (Taylor et al, 1998;Wolff and Rubin, 1998), Flamingo (Fmi) (Chae et al, 1999;Usui et al, 1999) and intracellular proteins like Disheveled (Dsh) (Theisen et al, 1994), Prickle (Pk) and Diego (Dgo) (Feiguin et al, 2001). In the Drosophila wing cells, all of those proteins are initially uniformly distributed in the whole cell membrane, however, upon mutual interactions they become asymmetrically segregated; Fz, Dsh and Dgo accumulate at the distal and Stbm/Vang and Pk at the proximal edge of the cell membrane (Axelrod, 2001;Strutt, 2001;Feiguin et al, 2001;Tree et al, 2002;Bastock et al, 2003).…”

“…In the Drosophila wing cells, all of those proteins are initially uniformly distributed in the whole cell membrane, however, upon mutual interactions they become asymmetrically segregated; Fz, Dsh and Dgo accumulate at the distal and Stbm/Vang and Pk at the proximal edge of the cell membrane (Axelrod, 2001;Strutt, 2001;Feiguin et al, 2001;Tree et al, 2002;Bastock et al, 2003). The atypical cadherin, Fmi resides on both distal and proximal edges, where it binds neighboring cells through heomophilic interactions (Usui et al, 1999;Shimada et al, 2001). Xenopus, zebrafish and the mouse, the same set of 'core PCP' proteins has been shown to regulate a plethora of early developmental events ranging from convergent extension movements during gastrulation, orientation of cochlear hair cell in the ear, neural tube closure, oriented cell division, lung branching, hair follicle alignment and polarized ciliary beating in the trachea and brain ventricles (Goodrich andStrutt, 2011, Gray et al, 2011;Zallen, 2007;Bosoi et al, 2011;De Marco et al, 2012;Kibar et al, 2009;Kibar et al, 2007;Rida and Chen, 2009;Wang and Nathans, 2007;Yates and Dean, 2007;Segalen and Bellaïche, 2009;Vladar et al, 2012) ( Fig.1.6.4.1).…”

Isoform‐specific interaction of Flamingo/Starry Night with excess Bazooka affects planar cell polarity in the Drosophila wing

“…So we analyzed whether either isoform could bind the PDZ domains of Bazooka by performing GST pull-down assays. A fusion protein comprising all three PDZ domains of Bazooka (Baz PDZ1-3 ) linked to GST was found to pull down a protein of the size predicted for Fmi/Stan (300 kDa; Usui et al, 1999) from lysates of wild-type wing discs (Fig. 1B).…”

“…1B). The anti-Fmi antibody used to detect this protein is directed against the extracellular domain (Usui et al, 1999), and should recognize both isoforms. We, therefore, tested Stan-and Fmitype proteins (fused to GST) separately for direct interaction with the Bazooka protein containing the three PDZ domains (translated in vitro).…”

“…Restriction of a given PCP protein to one or both of these domains depends on the function of the others (reviewed in Adler, 2002;Keller, 2002;Eaton, 2003;Fanto and McNeill, 2003;Strutt, 2003). The unconventional, seven-pass transmembrane cadherin Flamingo (Fmi), also known as Starry night (Stan), becomes restricted to both the proximal and distal cell boundaries, where it mediates homophilic adhesion (Chae et al, 1999;Usui et al, 1999). In addition, PCP proteins act at an earlier stage, during the development of the hexagonal shape of the cells.…”