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Fujita, Y., Nagaosa, K., Shiratsuchi, A., Nakanishi, Y. (2012). Role of NPxY motif in Draper-mediated apoptotic cell clearance in Drosophila.  Drug Discov. Ther. 6(6): 291--297.
FlyBase ID
FBrf0220536
Publication Type
Research paper
Abstract

Draper, a receptor responsible for the phagocytosis of apoptotic cells in Drosophila, possesses atypical epidermal growth factor (EGF)-like sequences in the extracellular region and the two phosphorylatable motifs NPxY and YxxL in the intracellular portion. We previously suggested that Pretaporter, a ligand for Draper, binds to the EGF-like repeat and augments the tyrosine phosphorylation of Draper. In this study, we first tested the binding of Pretaporter to various parts of the extracellular region of Draper and found that a single EGF-like sequence is sufficient for the binding. We next determined roles of the two intracellular motifs by forcedly expressing Draper proteins, in which tyrosine residues within the motifs had been substituted with phenylalanine, in hemocytes of Draper-lacking flies. We found that Draper proteins with Y-to-F substitution in either motif still underwent tyrosine phosphorylation, suggesting the occurrence of phosphorylation at both motifs. The Draper protein with substitution in the YxxL motif rescued a defect of phagocytosis, as did intact Draper, but the Draper protein with substitution in the NPxY motif did not, indicating a role of the motif NPxY, but not YxxL, in Draper-mediated phagocytosis. This coincides with our previous finding that Ced-6, an NPxY-binding signaling adaptor, is required for Draper's actions in apoptotic cell clearance. In summary, we demonstrated that Draper binds to its ligand Pretaporter using EGF-like sequences, and that the NPxY motif in the intracellular region of Draper plays an essential role in its actions as an engulfment receptor.

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    Language of Publication
    English
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    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Drug Discov. Ther.
    Title
    Drug discoveries & therapeutics
    ISBN/ISSN
    1881-7831 1881-784X
    Data From Reference
    Alleles (6)
    Genes (4)
    Physical Interactions (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (5)