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Structural changes in intermediate filament networks alter the activity of insulin‐degrading enzyme
Author(s) -
Chou Ying-Hao,
Kuo Wen-Liang,
Rosner Marsha Rich,
Tang Wei-Jen,
Goldman Robert D.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-137455
Subject(s) - protein filament , insulin , insulin degrading enzyme , enzyme , chemistry , medicine , biophysics , endocrinology , biochemistry , biology
ABSTRACT 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. FASEB J. 23, 3734–3742 (2009). www.fasebj.org