Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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}umassmed.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Glial Wingless/Wnt Regulates Glutamate Receptor Clustering and Synaptic Physiology at the Drosophila Neuromuscular Junction.
K. S. Kerr, Y. Fuentes-Medel, C. Brewer, R. Barria, J. Ashley, K. C. Abruzzi, A. Sheehan, O. E. Tasdemir-Yilmaz, M. R. Freeman, and V. Budnik (2014)
J. Neurosci. 34, 2910-2920
   Abstract »    Full Text »    PDF »
Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila.
S. H. Friedman, N. Dani, E. Rushton, and K. Broadie (2013)
Dis. Model. Mech. 6, 1400-1413
   Abstract »    Full Text »    PDF »
Receptor Tyrosine Kinases in the Nucleus.
G. Carpenter and H.-J. Liao (2013)
Cold Spring Harb Perspect Biol 5, a008979
   Abstract »    Full Text »    PDF »
Drosophila Heparan Sulfate 6-O-Endosulfatase Sulf1 Facilitates Wingless (Wg) Protein Degradation.
A. Kleinschmit, M. Takemura, K. Dejima, P. Y. Choi, and H. Nakato (2013)
J. Biol. Chem. 288, 5081-5089
   Abstract »    Full Text »    PDF »
Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction.
K. Kamimura, K. Ueno, J. Nakagawa, R. Hamada, M. Saitoe, and N. Maeda (2013)
J. Cell Biol. 200, 219-233
   Abstract »    Full Text »    PDF »
Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes.
H. Yu, X. Ye, N. Guo, and J. Nathans (2012)
Development 139, 4383-4394
   Abstract »    Full Text »    PDF »
Structure-Function Dissection of the Frizzled Receptor in Drosophila melanogaster Suggests Different Mechanisms of Action in Planar Polarity and Canonical Wnt Signaling.
D. Strutt, D. Madder, V. Chaudhary, and P. J. Artymiuk (2012)
Genetics 192, 1295-1313
   Abstract »    Full Text »    PDF »
Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions.
P.-I. Tsai, M. Wang, H.-H. Kao, Y.-J. Cheng, Y.-J. Lin, R.-H. Chen, and C.-T. Chien (2012)
PNAS 109, 17699-17704
   Abstract »    Full Text »    PDF »
Wnt Proteins.
K. Willert and R. Nusse (2012)
Cold Spring Harb Perspect Biol 4, a007864
   Abstract »    Full Text »    PDF »
WNTs in synapse formation and neuronal circuitry.
M. Park and K. Shen (2012)
EMBO J. 31, 2697-2704
   Abstract »    Full Text »    PDF »
Wnt Signaling in Neuromuscular Junction Development.
K. Koles and V. Budnik (2012)
Cold Spring Harb Perspect Biol 4, a008045
   Abstract »    Full Text »    PDF »
An Alternative Route for Nuclear mRNP Export by Membrane Budding.
B. Montpetit and K. Weis (2012)
Science 336, 809-810
   Abstract »    Full Text »    PDF »
Review: Lessons from in vitro studies and a related intracellular angiotensin II transgenic mouse model.
J. L. Cook and R. N. Re (2012)
Am J Physiol Regulatory Integrative Comp Physiol 302, R482-R493
   Abstract »    Full Text »    PDF »
Wnt Signaling in the Vertebrate Central Nervous System: From Axon Guidance to Synaptic Function.
P. C. Salinas (2012)
Cold Spring Harb Perspect Biol 4, a008003
   Abstract »    Full Text »    PDF »
Experimental Methods for Examining Synaptic Plasticity in Drosophila.
D. P. Olsen and H. Keshishian (2012)
Cold Spring Harb Protoc 2012, pdb.top067785
   Abstract »    Full Text »    PDF »
From Synapse to Nucleus and Back Again--Communication over Distance within Neurons.
M. Fainzilber, V. Budnik, R. A. Segal, and M. R. Kreutz (2011)
J. Neurosci. 31, 16045-16048
   Abstract »    Full Text »    PDF »
Expression of a naturally occurring angiotensin AT1 receptor cleavage fragment elicits caspase-activation and apoptosis.
J. L. Cook, A. Singh, D. deHaro, J. Alam, and R. N. Re (2011)
Am J Physiol Cell Physiol 301, C1175-C1185
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXX. The Class Frizzled Receptors.
G. Schulte (2010)
Pharmacol. Rev. 62, 632-667
   Abstract »    Full Text »    PDF »
Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap.
J. Rohrbough and K. Broadie (2010)
Development 137, 3523-3533
   Abstract »    Full Text »    PDF »
Internalization and Trafficking Assay for Drosophila Larvae.
P. Ramachandran and V. Budnik (2010)
Cold Spring Harb Protoc 2010, pdb.prot5472
   Abstract »    Full Text »    PDF »
Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.
D. Calebiro, V. O. Nikolaev, and M. J. Lohse (2010)
J. Mol. Endocrinol. 45, 1-8
   Abstract »    Full Text »    PDF »
Synaptic Homeostasis Is Consolidated by the Cell Fate Gene gooseberry, a Drosophila pax3/7 Homolog.
B. Marie, E. Pym, S. Bergquist, and G. W. Davis (2010)
J. Neurosci. 30, 8071-8082
   Abstract »    Full Text »    PDF »
To build a synapse: signaling pathways in neuromuscular junction assembly.
H. Wu, W. C. Xiong, and L. Mei (2010)
Development 137, 1017-1033
   Abstract »    Full Text »    PDF »
Presynaptic Local Signaling by a Canonical Wingless Pathway Regulates Development of the Drosophila Neuromuscular Junction.
C. Miech, H.-U. Pauer, X. He, and T. L. Schwarz (2008)
J. Neurosci. 28, 10875-10884
   Abstract »    Full Text »    PDF »
Inactivation of nuclear Wnt-{beta}-catenin signaling limits blastocyst competency for implantation.
H. Xie, S. Tranguch, X. Jia, H. Zhang, S. K. Das, S. K. Dey, C. J. Kuo, and H. Wang (2008)
Development 135, 717-727
   Abstract »    Full Text »    PDF »
Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation.
J. Rohrbough, E. Rushton, E. Woodruff III, T. Fergestad, K. Vigneswaran, and K. Broadie (2007)
Genes & Dev. 21, 2607-2628
   Abstract »    Full Text »    PDF »
{beta}-Catenin Regulates Acetylcholine Receptor Clustering in Muscle Cells through Interaction with Rapsyn.
B. Zhang, S. Luo, X.-P. Dong, X. Zhang, C. Liu, Z. Luo, W.-C. Xiong, and L. Mei (2007)
J. Neurosci. 27, 3968-3973
   Abstract »    Full Text »    PDF »
Diverse pathways for nuclear signaling by G protein-coupled receptors and their ligands.
E. J. Goetzl (2007)
FASEB J 21, 638-642
   Abstract »    Full Text »    PDF »
Postsynaptic Membrane Addition Depends on the Discs-Large-Interacting t-SNARE Gtaxin.
D. Gorczyca, J. Ashley, S. Speese, N. Gherbesi, U. Thomas, E. Gundelfinger, L. S. Gramates, and V. Budnik (2007)
J. Neurosci. 27, 1033-1044
   Abstract »    Full Text »    PDF »
An Unconventional Nuclear Localization Motif Is Crucial for Function of the Drosophila Wnt/Wingless Antagonist Naked Cuticle.
S. Waldrop, C.-C. Chan, T. Cagatay, S. Zhang, R. Rousset, J. Mack, W. Zeng, M. Fish, M. Zhang, M. Amanai, et al. (2006)
Genetics 174, 331-348
   Abstract »    Full Text »    PDF »
Novel function of {beta}-arrestin2 in the nucleus of mature spermatozoa.
E. M. Neuhaus, A. Mashukova, J. Barbour, D. Wolters, and H. Hatt (2006)
J. Cell Sci. 119, 3047-3056
   Abstract »    Full Text »    PDF »
Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP.
B. Ataman, J. Ashley, D. Gorczyca, M. Gorczyca, D. Mathew, C. Wichmann, S. J. Sigrist, and V. Budnik (2006)
PNAS 103, 7841-7846
   Abstract »    Full Text »    PDF »
CELL SIGNALING: Frizzled at the Cutting Edge of the Synapse.
A. Martinez Arias (2005)
Science 310, 1284-1285
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882