title: Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2.
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.
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Mathew
authors.forename: Bulent
authors.initials: B
authors.lastname: Ataman
authors.forename: Jinyun
authors.initials: J
authors.lastname: Chen
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Susan
authors.initials: S
authors.lastname: Cumberledge
authors.forename: Vivian
authors.initials: V
authors.lastname: Budnik
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D051157:Frizzled Receptors; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009469:Neuromuscular Junction / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013570:Synaptic Membranes / Q000378:metabolism; D014162:Transfection; D019076:Transgenes; D051155:Wnt1 Protein
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051155:Wnt1 Protein; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila