Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling.
Acquisition of planar cell polarity (PCP) in epithelia involves intercellular communication, during which cells align their polarity with that of their neighbors. The transmembrane proteins Frizzled (Fz) and Van Gogh (Vang) are essential components of the intercellular communication mechanism, as loss of either strongly perturbs the polarity of neighboring cells. How Fz and Vang communicate polarity information between neighboring cells is poorly understood. The atypical cadherin, Flamingo (Fmi), is implicated in this process, yet whether Fmi acts permissively as a scaffold or instructively as a signal is unclear. Here, we provide evidence that Fmi functions instructively to mediate Fz-Vang intercellular signal relay, recruiting Fz and Vang to opposite sides of cell boundaries. We propose that two functional forms of Fmi, one of which is induced by and physically interacts with Fz, bind each other to create cadherin homodimers that signal bidirectionally and asymmetrically, instructing unequal responses in adjacent cell membranes to establish molecular asymmetry.
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Wei-Shen
WS
Chen
Dragana
D
Antic
Maja
M
Matis
Catriona Y
CY
Logan
Michael
M
Povelones
Graham A
GA
Anderson
Roel
R
Nusse
Jeffrey D
JD
Axelrod
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D016764:Cell Polarity; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D025941:Protein Interaction Mapping; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
D015820:Cadherins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; C111638:Vang protein, Drosophila; C058784:fz protein, Drosophila; C121420:stan protein, Drosophila