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Yatsenko, A.S., Gray, E.E., Shcherbata, H.R., Patterson, L.B., Sood, V.D., Kucherenko, M.M., Baker, D., Ruohola-Baker, H. (2007). A putative Src homology 3 domain binding motif but not the C-terminal dystrophin WW domain binding motif is required for dystroglycan function in cellular polarity in Drosophila.  J. Biol. Chem. 282(20): 15159--15169.
FlyBase ID
FBrf0191923
Publication Type
Research paper
Abstract

The conserved dystroglycan-dystrophin (Dg.Dys) complex connects the extracellular matrix to the cytoskeleton. In humans as well as Drosophila, perturbation of this complex results in muscular dystrophies and brain malformations and in some cases cellular polarity defects. However, the regulation of the Dg.Dys complex is poorly understood in any cell type. We now find that in loss-of-function and overexpression studies more than half (34 residues) of the Dg proline-rich conserved C-terminal regions can be truncated without significantly compromising its function in regulating cellular polarity in Drosophila. Notably, the truncation eliminates the WW domain binding motif at the very C terminus of the protein thought to mediate interactions with dystrophin, suggesting that a second, internal WW binding motif can also mediate this interaction. We confirm this hypothesis by using a sensitive fluorescence polarization assay to show that both WW domain binding sites of Dg bind to Dys in humans (K(d) = 7.6 and 81 microM, respectively) and Drosophila (K(d) = 16 and 46 microM, respectively). In contrast to the large deletion mentioned above, a single proline to an alanine point mutation within a predicted Src homology 3 domain (SH3) binding site abolishes Dg function in cellular polarity. This suggests that an SH3-containing protein, which has yet to be identified, functionally interacts with Dg.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference
    Aberrations (1)
    Alleles (15)
    Genes (7)
    Physical Interactions (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (12)