The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b

Kazunari Yamashita, Atsushi Suzuki, Yoshinori Satoh, Mariko Ide, Yoshiko Amano, Maki Masuda-Hirata, Yukiko K. Hayashi, Keisuke Hamada, Kazuhiro Ogata, Shigeo Ohno

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Utrophin is a widely expressed paralogue of dystrophin, the protein responsible for Duchenne muscular dystrophy. Utrophin is a large spectrin-like protein whose C-terminal domain mediates anchorage to a laminin receptor, dystroglycan (DG). The rod domain, composed of 22 spectrin-like repeats, connects the N-terminal actin-binding domain and the C-terminal DG binding domain, and thus mediates molecular linkage between intracellular F-actin and extracellular basement membrane. Previously, we demonstrated that a cell polarity-regulating kinase, PAR-1b, interacts with the utrophin-DG complex, and positively regulates the interaction between utrophin and DG. In this study, we demonstrate that the 8th and 9th spectrin-like repeats (R8 and R9) of utrophin cooperatively form a PAR-1b-interacting domain, and that Ser1258 within R9 is specifically phosphorylated by PAR-1b. Substitution of Ser1258 to alanine reduces the interaction between utrophin and DG, suggesting that the Ser1258 phosphorylation contributes to the stabilization of the utrophin-DG complex. Interestingly, PAR-1b also binds and phosphorylates R8-9 of dystrophin, and colocalizes with dystrophin at the skeletal muscle membrane. These results reveal a novel function of the rod domain of utrophin beyond that of a passive structural linker connecting the N- and C-terminal domain.

Original languageEnglish
Pages (from-to)812-817
Number of pages6
JournalBiochemical and biophysical research communications
Volume391
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

Keywords

  • Dystroglycan
  • Dystrophin
  • Laminin
  • PAR-1
  • Spectrin-like repeat
  • Utrophin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b'. Together they form a unique fingerprint.

Cite this