GSBS Student Publications

Title

Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP

Student Author(s)

Bulent Ataman; James Ashley

GSBS Program

Neuroscience

UMMS Affiliation

Department of Neurobiology; Budnik Lab; Graduate School of Biomedical Sciences, Neuroscience Program

Date

5-10-2006

Document Type

Article

Medical Subject Headings

Active Transport, Cell Nucleus; Animals; Carrier Proteins; Cell Nucleus; Drosophila Proteins; Drosophila melanogaster; Frizzled Receptors; Larva; Nerve Tissue Proteins; Neuromuscular Junction; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled; Signal Transduction; Synapses; Synaptic Vesicles; Two-Hybrid System Techniques; Wnt1 Protein

Disciplines

Neuroscience and Neurobiology

Abstract

The Wingless pathway plays an essential role during synapse development. Recent studies at Drosophila glutamatergic synapses suggest that Wingless is secreted by motor neuron terminals and binds to postsynaptic Drosophila Frizzled-2 (DFz2) receptors. DFz2 is, in turn, endocytosed and transported to the muscle perinuclear area, where it is cleaved, and the C-terminal fragment is imported into the nucleus, presumably to regulate transcription during synapse growth. Alterations in this pathway interfere with the formation of new synaptic boutons and lead to aberrant synaptic structures. Here, we show that the 7 PDZ protein dGRIP is necessary for the trafficking of DFz2 to the nucleus. dGRIP is localized to Golgi and trafficking vesicles, and dgrip mutants mimic the synaptic phenotypes observed in wg and dfz2 mutants. DFz2 and dGRIP colocalize in trafficking vesicles, and a severe decrease in dGRIP levels prevents the transport of endocytosed DFz2 receptors to the nucleus. Moreover, coimmunoprecipitation experiments in transfected cells and yeast two-hybrid assays suggest that the C terminus of DFz2 interacts directly with the PDZ domains 4 and 5. These results provide a mechanism by which DFz2 is transported from the postsynaptic membrane to the postsynaptic nucleus during synapse formation and implicate dGRIP as an essential molecule in the transport of this signal.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7841-6. Epub 2006 May 8. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

16682643