Expression of integrin alpha 1 beta 1 is regulated by nerve growth factor and dexamethasone in PC12 cells. Functional consequences for adhesion and neurite outgrowth.
PC12 cells respond to nerve growth factor by differentiating into sympathetic neuron-like cells that employ the integrin alpha 1 beta 1 to attach to, and extend neurites on, substrata coated with collagen or laminin. In one PC12 subline, PC12i, prolonged treatment with nerve growth factor results in a marked increase in synthesis of alpha 1 subunits and in the level of alpha 1 mRNA, with a corresponding increase in alpha 1 beta 1 expressed on the cell surface. These changes are accompanied by substantial increases in initial cell attachment to collagen and in the fraction of neurite-bearing cells and average neurite length. Integrin beta 1-subunits are constitutively expressed, so that alpha 1 synthesis controls the amount of alpha 1 beta 1 heterodimer expressed on PC12i cells. Acidic fibroblast growth factor also induces alpha 1 beta 1 in PC12i cells, with consequent enhancement of neurite outgrowth; treatment with epidermal growth factor or dibutyryl cyclic AMP does not have these effects. Another subline, PC12c, expresses high levels of alpha 1 mRNA and alpha 1 protein constitutively. With or without nerve growth factor pretreatment, these cells adhere well to collagen and a majority extend neurites when replated in the presence of nerve growth factor. Dexamethasone treatment of PC12c cells reduces expression of alpha 1 mRNA and alpha 1 protein, with consequent reduction in attachment to collagen. In both sublines, then, there is a direct relationship between the level of a specific matrix receptor and cell-matrix adhesion. Moreover, our results suggest that induced expression of this matrix receptor is an essential aspect of the regulation of neurite extension by nerve growth factor in PC12i cells.
Zhang
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Department of Biochemistry and Molecular Biology, State University of New York Health Science Center, Syracuse 13210.
Tarone
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Turner
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D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D009414:Nerve Growth Factors / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006133:Growth Substances; D016023:Integrins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003907:Dexamethasone