Regulation of Bin1 SH3 domain binding by phosphoinositides

Chie Kojima, Ari Hashimoto, Izumi Yabuta, Mayumi Hirose, Shigeru Hashimoto, Yasunori Kanaho, Hideki Sumimoto, Takahisa Ikegami, Hisataka Sabe

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Bin1/M-amphiphysin-II is an amphiphysin-II isoform highly expressed in transverse tubules of adult striated muscle and is implicated in their biogenesis. Bin1 contains a basic unique amino-acid sequence, Exon10, which interacts with certain phosphoinositides such as phosphatidylinositol-4,5- bisphosphate (PI(4,5)P2), to localize to membranes. Here we found that Exon10 also binds to the src homology 3 (SH3) domain of Bin1 itself, and hence blocks the binding of the SH3 domain to its canonical PxxP ligands, including dynamin. This blockage was released by addition of PI(4,5) P 2 in vitro or in cells overexpressing phosphatidylinositol 4-phosphate 5-kinase. The Exon10-binding interface of the Bin1 SH3 domain largely overlapped with its PxxP-binding interface. We also show that the PLCδ pleckstrin homology domain, another PI(4,5)P2-binding module, cannot substitute for Exon10 in Bin1 function in transverse tubule formation, and suggest the importance of the dual biochemical properties of Exon10 in myogenesis. Our results exemplify a novel mechanism of SH3 domain regulation, and suggest that the SH3-mediated protein-protein interactions of Bin1 are regulated by Exon10 so that it may only occur when Bin1 localizes to certain submembrane areas.

Original languageEnglish
Pages (from-to)4413-4422
Number of pages10
JournalEMBO Journal
Volume23
Issue number22
DOIs
Publication statusPublished - Nov 10 2004

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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