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Insulin‐like growth factor binding protein‐1 activates integrin‐mediated intracellular signaling and migration in oligodendrocytes
Author(s) -
Chesik Daniel,
De Keyser Jacques,
Bron Reinier,
Fuhler Gwenny M.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06703.x
Subject(s) - microbiology and biotechnology , focal adhesion , biology , integrin , ptk2 , signal transduction , growth factor , intracellular , actin cytoskeleton , protein kinase c , receptor , mitogen activated protein kinase kinase , biochemistry , cytoskeleton , cell
J. Neurochem. (2010) 113 , 1319–1330. Abstract 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.