© 2005 The Japanese Biochemical Society
Regular Paper |
Ubiquitin-Interacting Motifs of Epsin Are Involved in the Regulation of Insulin-Dependent Endocytosis
Departments of 1 Biochemistry and 2 Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551
To whom correspondence should be addressed. Tel: +81-82-257-5130, Fax: +81-82-257-5134, E-mail: akikuchi{at}hiroshima-u.ac.jp
ABSTRACT
Epsin is a key molecule in receptor-mediated endocytosis. Epsin is phosphorylated and ubiquitinated, and these post-translational modifications are necessary for the regulation of endocytosis. Since human Epsin (hEpsin) has two ubiquitin-interacting motifs (UIMs), we investigated the roles of these UIMs in endocytosis. hEpsin formed a complex with ubiquitinated proteins but did not bind to monoubiquitin. Neither of the two UIMs of hEpsin alone was sufficient to form a complex with ubiquitinated proteins: both UIMs were necessary. Mutations of Asp209 and Asp210 to Ala in UIM (hEpsinDA) abolished the binding activity of hEpsin to ubiquitinated proteins. However, hEpsinDA interacted with Eps15, POB1, and AP-2, which are involved in receptor-mediated endocytosis, as efficiently as wild-type hEpsin. Expression of hEpsinDA in CHO-IR cells affected neither the binding of insulin to nor insulin-dependent autophosphorylation of its receptor. Expression of wild-type hEpsin inhibited the internalization of insulin, whereas that of hEpsinDA did not. These results suggest that the UIM motifs of hEpsin interact with proteins modified with ubiquitin, and that the complex formation is involved in insulin-dependent receptor endocytosis.
FOOTNOTES
* Present address: Department of Pathophysiology, Shujitsu University School, Okayama 703-8516.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Chen and X. Zhuang Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus PNAS, August 19, 2008; 105(33): 11790 - 11795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Musch, A. B. Puffer, and L. Goldstein Volume expansion stimulates monoubiquitination and endocytosis of surface-expressed skate anion-exchanger isoform Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1657 - R1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Barriere, C. Nemes, K. Du, and G. L. Lukacs Plasticity of Polyubiquitin Recognition as Lysosomal Targeting Signals by the Endosomal Sorting Machinery Mol. Biol. Cell, October 1, 2007; 18(10): 3952 - 3965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Traub and G. L. Lukacs Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs J. Cell Sci., February 15, 2007; 120(4): 543 - 553. [Abstract] [Full Text] [PDF]
|
|