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.

Abstract

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.