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Citation
Ataman, B., Ashley, J., Gorczyca, D., Gorczyca, M., Mathew, D., Wichmann, C., Sigrist, S.J., Budnik, V. (2006). Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP.  Proc. Natl. Acad. Sci. U.S.A. 103(20): 7841--7846.
FlyBase ID
FBrf0195116
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC1472532 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (12)
    Genes (13)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (7)
    Experimental Tools (2)
    Transgenic Constructs (5)