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The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function

Author

  • A. S. Yatsenko
  • M. M. Kucherenko
  • M. Pantoja
  • K. A. Fischer
  • J. Madeoy
  • W-M Deng
  • Martina Schneider
  • Stefan Baumgartner
  • J. Akey
  • H. R. Shcherbata
  • H. Ruohola-Baker

Summary, in English

Background: Dystroglycan (Dg) is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC) which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C-terminal PPXY motif has been established as a binding site for Dystrophin (Dys) WW-domain. However, our previous studies indicate that both Dystroglycan PPXY motives, WWbsI and WWbsII can bind Dystrophin protein in vitro. Results: We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required. Conclusion: Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.

Department/s

  • Invertebrate Developmental Biology, Stefan Baumgartner's group

Publishing year

2009

Language

English

Publication/Series

BMC Developmental Biology

Volume

9

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Developmental Biology

Status

Published

Research group

  • Invertebrate Developmental Biology, Stefan Baumgartner's group

ISBN/ISSN/Other

  • ISSN: 1471-213X