HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Buy All Versions of this Article: fj.09-137455v1 23/11/3734    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Chou, Y.-H. Articles by Goldman, R. D. PubMed PubMed Citation Articles by Chou, Y.-H. Articles by Goldman, R. D.

Structural changes in intermediate filament networks alter the activity of insulin-degrading enzyme

Ying-Hao Chou^*, Wen-Liang Kuo, Marsha Rich Rosner, Wei-Jen Tang and Robert D. Goldman^*,1

^* Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois, USA; and

Section of Hematology/Oncology, Department of Medicine, and

Ben-May Institute for Cancer Research, University of Chicago, Chicago, Illinois, USA

¹ Correspondence: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Ave., Chicago, IL 60611. E-mail: r-goldman{at}northwestern.edu

The intermediate filament (IF) protein nestin coassembles with vimentin and promotes the disassembly of these copolymers when vimentin is hyperphosphorylated during mitosis. The aim of this study is to determine the function of these nonfilamentous particles by identifying their interacting partners. In this study, we report that these disassembled vimentin/nestin complexes interact with insulin degrading enzyme (IDE). Both vimentin and nestin interact with IDE in vitro, but vimentin binds IDE with a higher affinity than nestin. Although the interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser-55, the interaction between nestin and IDE is phosphorylation independent. Further analyses show that phosphorylated vimentin plays the dominant role in targeting IDE to the vimentin/nestin particles in vivo, while the requirement for nestin is related to its ability to promote vimentin IF disassembly. The binding of IDE to either nestin or phosphorylated vimentin regulates IDE activity differently, depending on the substrate. The insulin degradation activity of IDE is suppressed 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2- to 3-fold. Taken together, our data demonstrate that the nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE.—Chou, Y.-H., Kuo, W.-L., Rich Rosner, M., Tang, W.-J., Goldman, R. D. Structural changes in intermediate filament networks alter the activity of insulin-degrading enzyme.

Key Words: phosphorylation • metalloprotease • cytoskeleton

This article has been cited by other articles:

				J. E. Carpenter, W. Jackson, G. A. de Souza, L. Haarr, and C. Grose Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum J. Virol., January 15, 2010; 84(2): 847 - 855. [Abstract] [Full Text] [PDF]