Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95.
In Drosophila, the frizzled gene plays a critical role in the establishment of tissue polarity, but the function of the Frizzled family of proteins in mammals is largely unknown. Recent evidence suggested that Frizzleds are receptors for the Wnt family of secreted glycoproteins which are involved in cell fate determination. However, it is unclear how Frizzled receptors transduce Wnt signals to intracellular signaling components. Here we show that the mouse Frizzled-1, -2, -4 and -7 can bind to proteins of the PSD-95 family, which are implicated in the assembly and localization of multiprotein signaling complexes in the brain. Moreover, PSD-95 can form a ternary complex with Frizzled-2 and the adenomatous polyposis coli protein, a negative regulator of Wnt signaling, suggesting that members of the PSD-95 family may serve to recruit intracellular signaling molecules of the Wnt/Frizzled pathway into the vicinity of the receptor.
Hering
Heike
H
Center for Learning and Memory, Howard Hughes Medical Institute, RIKEN-MIT Neuroscience Research Center, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue (E18-215), Cambridge, MA 02139, USA.
Sheng
Morgan
M
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D051157:Frizzled Receptors; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C489740:FZD1 protein, human; C489742:FZD2 protein, human; D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse; C489743:Fzd2 protein, mouse; C498581:Fzd4 protein, mouse; C492041:Fzd7 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; C033652:postsynaptic density proteins; D051528:Guanylate Kinases