Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2

Science. 2005 Nov 25;310(5752):1344-7. doi: 10.1126/science.1117051.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Nucleus / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Endocytosis
  • Frizzled Receptors
  • Molecular Sequence Data
  • Muscle Cells / metabolism
  • Mutagenesis, Site-Directed
  • Neuromuscular Junction / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter / chemistry
  • Receptors, Neurotransmitter / genetics
  • Receptors, Neurotransmitter / metabolism*
  • Signal Transduction*
  • Synaptic Membranes / metabolism
  • Transfection
  • Transgenes
  • Wnt1 Protein

Substances

  • Drosophila Proteins
  • Frizzled Receptors
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter
  • Wnt1 Protein
  • fz2 protein, Drosophila
  • wg protein, Drosophila