CELL-CYCLE PHASE-SPECIFIC SURFACE EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS TRKA AND P75(NTR)

Expression of the nerve growth factor (NGF) receptors TrkA and p75(NTR ) was found to vary at the surface of PC12 cells in a cell cycle phase -specific manner. This was evidenced by using flow cytometric and micr oscopic analysis of cell populations labeled with antibodies to the ex tracellular domains of both receptors. Differential expression of thes e receptors also was evidenced by biotinylation of surface proteins an d Western analysis, using antibodies specific for the extracellular do mains of TrkA and p75(NTR). TrkA is expressed most strongly at the cel l surface in M and early G1 phases, whereas p75(NTR) is expressed main ly in late G1, S, and G2 phases. This expression reflects the molecula r and cellular responses to NGF in specific phases of the cell cycle; in the G1 phase NGF elicits both the anti-mitogenic effect, i.e., inhi bition of the G1 to S transition, and the differentiation response whe reas a survival effect is provoked elsewhere in the cell cycle. A mode l is proposed relating these responses to the surface expression of th e two receptors. These observations open the way for novel approaches to the investigation of the mechanism of NGF signal transduction.