Publication

Insulin-like growth factor binding protein-1 activates integrin-mediated intracellular signaling and migration in oligodendrocytes

Chesik, D., De Keyser, J., Bron, R. & Fuhler, G. M., Jun-2010, In : Journal of Neurochemistry. 113, 5, p. 1319-1330 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

P>In multiple sclerosis (MS), oligodendrocytes in lesions are lost, leaving damaged tissue virtually devoid of these myelin-producing cells. Our group has recently demonstrated enhanced expression of insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) in oligodendrocytes (CNPase+) localized adjacent to MS lesions. In the present study, we demonstrate IGF-1-independent actions of IGFBP-1 on OLN-93 oligodendroglial cells, including activation of kinases ERK1/2, focal adhesion kinase and p21-activated kinase as well as small monomeric GTPases Rac and Ral. Activation of these intracellular signaling components was inhibited by GRGDS peptide, indicating signaling through integrin receptors. While both IGF-1 and IGFBP-1 demonstrated rapid induction of actin polymerization, IGFBP-1 proved to be a more potent inducer of migration than IGF-1, inducing a threefold increased migration rate. Furthermore, through integrin receptor signaling IGFBP-1 induced rapid transient translocalization of intracellular Rac toward punctuated structures followed by translocation of Rac to the plasma membrane. Our results suggest that up-regulation of IGFBP-1 in oligodendrocytes in MS may serve two functions: (i) regulate IGF-1 actions, (ii) exert IGF-independent effects through its RGD sequence.

Original languageEnglish
Pages (from-to)1319-1330
Number of pages12
JournalJournal of Neurochemistry
Volume113
Issue number5
Publication statusPublished - Jun-2010

    Keywords

  • insulin-like growth factor, multiple sclerosis, remyelination, CENTRAL-NERVOUS-SYSTEM, HUMAN TROPHOBLAST MIGRATION, IN-VIVO ACTIONS, MULTIPLE-SCLEROSIS, CELL-MIGRATION, IGF-I, ALPHA-5-BETA-1 INTEGRIN, TRANSGENIC MICE, MYELINATION, MYELODYSPLASIA

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