Embryonic neurons adapt to the inhibitory proteoglycan aggrecan by increasing integrin expression.

Abstract	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 alpha6beta1 and alpha3beta1, 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.
Authors	M L Condic, D M Snow, P C Letourneau
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 19 Issue 22 Pg. 10036-43 (Nov 15 1999) ISSN: 1529-2401 [Electronic] United States
PMID	10559411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Aggrecans Chondroitin Sulfate Proteoglycans Extracellular Matrix Proteins Integrin alpha3beta1 Integrin alpha6beta1 Integrins Lectins, C-Type Proteoglycans
Topics	Aggrecans Animals Cells, Cultured Chick Embryo Chondroitin Sulfate Proteoglycans (pharmacology) Extracellular Matrix Proteins Ganglia, Spinal (cytology, embryology) Gene Expression Regulation (drug effects, physiology) Integrin alpha3beta1 Integrin alpha6beta1 Integrins (genetics) Lectins, C-Type Neurites (physiology) Neurons (cytology, drug effects, physiology) Protein Biosynthesis Proteoglycans (pharmacology) Transcription, Genetic

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