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Interaction between serine phosphorylated IRS‐1 and β1‐integrin affects the stability of neuronal processes
Author(s) -
Wang Jin Ying,
Gualco Elisa,
Peruzzi Francesca,
Sawaya Bassel E.,
Passiatore Giovanni,
Marcinkiewicz Cezary,
Staniszewska Izabella,
Ferrante Pasquale,
Amini Shohreh,
Khalili Kamel,
Reiss Krzysztof
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21400
Subject(s) - integrin , phosphorylation , microbiology and biotechnology , receptor , chemistry , serine , tumor necrosis factor alpha , insulin receptor , biology , insulin , endocrinology , biochemistry , insulin resistance
Tumor necrosis factor‐α (TNFα) released in the brain by HIV‐activated macrophages/microglia is suspected to compromise neuronal survival. Previously, we have demonstrated that activated receptor for insulin‐like growth factor I (IGF‐IR) protects neurons from TNFα‐induced neuronal damage (Wang et al. [ 2006] J. Neurosci. Res. 83:7–18). Because TNFα triggers phosphorylation of insulin receptor substrate 1 (IRS‐1) on serine residues (pS‐IRS‐1; Rui et al. [ 2001] J. Clin. Invest. 107:181–189), and pS‐IRS‐1 binds integrins (Reiss et al. [ 2001] Oncogene 20:490–500), we asked how these events affect neuronal processes. We show that β1‐integrin and pS‐IRS‐1 colocalize in PC12 cells and in primary cortical neurons. TNFα treatment elevated membrane‐associated pS‐IRS‐1, enhanced pS‐IRS‐1 interaction with β1‐integrin, and attenuated cell attachment to collagen IV. In contrast, IGF‐I inhibited pS‐IRS‐1–β1‐integrin complexes and improved cell attachment. The domain of IRS‐1 involved in β1‐integrin binding mapped between amino acids 426 and 740, and the expression of 426–740/IRS‐1 mutant attenuated neuronal outgrowth. Our results indicate that TNFα facilitates the interaction of pS‐IRS‐1 and β1‐integrin and destabilizes neuronal processes. IGF‐I counteracts TNFα‐mediated accumulation of pS‐IRS‐1–β1‐integrin complexes supporting the stability of neuronal processes. © 2007 Wiley‐Liss, Inc.