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The Journal of Neuroscience, November 15, 1999, 19(22):10036-10043

Embryonic Neurons Adapt to the Inhibitory Proteoglycan Aggrecan by Increasing Integrin Expression

Maureen L. Condic¹, Diane M. Snow², and Paul C. Letourneau³

¹ Department of Neurobiology and Anatomy, University of Utah, School of Medicine, Salt Lake City, Utah 84132-0002, ² Department of Anatomy and Neurobiology, The University of Kentucky, Lexington, Kentucky 40536-0298, and ³ Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455

The primary mediators of cell migration during development, wound healing and metastasis, are receptors of the integrin family. In the developing and regenerating nervous system, chondroitin sulfate proteoglycans (CSPGs) inhibit the integrin-dependent migration of neuronal growth cones. Here we report that embryonic sensory neurons cultured on the growth-promoting molecule laminin in combination with the inhibitory CSPG aggrecan rapidly adapt to inhibition. Adaptation is associated with a two- to threefold increase in the levels of RNA and surface protein for two laminin receptors, integrin 61 and 31, indicating that integrin expression is regulated by aggrecan. Increased integrin expression is associated both with increases in neuronal cell adhesion/outgrowth and with decreases in the ability of aggrecan to inhibit cell adhesion. Directly increasing integrin expression by adenoviral infection is sufficient to eliminate the inhibitory effects of aggrecan, indicating that upregulation of integrin receptors may promote neuronal regeneration in the presence of inhibitory matrix components.

Key words: integrin; CSPG; aggrecan; adaptation to inhibition; proteoglycan; regeneration; adenovirus-mediated gene transfer

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Copyright © 1999 Society for Neuroscience  0270-6474/99/192210036-08$05.00/0

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