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PMID: 15483625 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of Bin1 SH3 domain binding by phosphoinositides.

The EMBO journal ·Vol. 23 ·No. 22 ·2004-11-10 ·Pages 4413-22

Kojima C, Hashimoto A, Yabuta I, Hirose M, Hashimoto S, Kanaho Y, Sumimoto H, Ikegami T, Sabe H

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)P(2)), 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 PLCdelta pleckstrin homology domain, another PI(4,5)P(2)-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.

MeSH Terms
Adaptor Proteins, Signal Transducing Adenoviridae/genetics Alternative Splicing Amino Acid Sequence Animals COS Cells Carrier Proteins/chemistry,genetics,metabolism Chlorocebus aethiops Dynamins/antagonists & inhibitors Glutathione Transferase/metabolism Humans Ligands Models, Molecular Muscle Development Mutation Nuclear Magnetic Resonance, Biomolecular Nuclear Proteins/chemistry,genetics,metabolism Phosphatidylinositols/metabolism Phosphotransferases (Alcohol Group Acceptor)/metabolism Protein Binding Protein Isoforms/chemistry,genetics,metabolism Protein Structure, Tertiary RNA, Small Interfering/metabolism Signal Transduction Tumor Suppressor Proteins/chemistry,genetics,metabolism src Homology Domains/genetics
Chemicals
Adaptor Proteins, Signal Transducing BIN1 protein, human Carrier Proteins Ligands Nuclear Proteins Phosphatidylinositols Protein Isoforms RNA, Small Interfering Tumor Suppressor Proteins Glutathione Transferase Phosphotransferases (Alcohol Group Acceptor) 1-phosphatidylinositol-4-phosphate 5-kinase Dynamins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kojima Chie
Department of Molecular Biology, Osaka Bioscience Institute, Suita, Japan.
Hashimoto Ari
Yabuta Izumi
Hirose Mayumi
Hashimoto Shigeru
Kanaho Yasunori
Sumimoto Hideki
Ikegami Takahisa
Sabe Hisataka
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2004-11-10
Epub
2004-00-14
Pages
4413-22
Language
English
Region
England
NLM ID
8208664
PMCID
PMC526460
Subset
IM
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