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Science 310 (5752): 1344-1347

Copyright © 2005 by the American Association for the Advancement of Science

Wingless Signaling at Synapses Is Through Cleavage and Nuclear Import of Receptor DFrizzled2

Dennis Mathew,1 Bulent Ataman,1 Jinyun Chen,2 Yali Zhang,2 Susan Cumberledge,2 Vivian Budnik1*

Abstract: Wingless secretion provides pivotal signals during development by activating transcription of target genes. At Drosophila synapses, Wingless is secreted from presynaptic terminals and is required for synaptic growth and differentiation. Wingless binds the seven-pass transmembrane DFrizzled2 receptor, but the ensuing events at synapses are not known. We show that DFrizzled2 is endocytosed from the postsynaptic membrane and transported to the nucleus. The C terminus of DFrizzled2 is cleaved and translocated into the nucleus; the N-terminal region remains just outside the 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 transduction occurs through the nuclear localization of DFrizzled2-C for potential 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}

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