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Wingless Signaling at Synapses Is Through Cleavage and Nuclear Import of Receptor DFrizzled2
Dennis Mathew,1Bulent Ataman,1Jinyun Chen,2Yali Zhang,2Susan Cumberledge,2Vivian Budnik1*
Wingless secretion provides pivotal signals during developmentby activating transcription of target genes. At Drosophila synapses,Wingless is secreted from presynaptic terminals and is requiredfor synaptic growth and differentiation. Wingless binds theseven-pass transmembrane DFrizzled2 receptor, but the ensuingevents at synapses are not known. We show that DFrizzled2 isendocytosed from the postsynaptic membrane and transported tothe nucleus. The C terminus of DFrizzled2 is cleaved and translocatedinto the nucleus; the N-terminal region remains just outsidethe nucleus. Translocation of DFrizzled2-C into the nucleus,but not its cleavage and transport, depends on Wingless signaling.We conclude that, at synapses, Wingless signal transductionoccurs through the nuclear localization of DFrizzled2-C forpotential transcriptional regulation of synapse development.
1 Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA. 2 Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA.
* To whom correspondence should be addressed. E-mail: vivian.budnik{at}umassmed.edu
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