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The Journal of Neuroscience, September 1, 1998, 18(17):6767-6775

Cell Cycle Phase-Specific Surface Expression of Nerve Growth Factor Receptors TrkA and p75^NTR

José Luis Urdiales¹, Elena Becker², Muriel Andrieu¹, Annie Thomas¹, Jérôme Jullien¹, Leo A. van Grunsven¹, Sophie Menut¹, Gerard I. Evan³, Dionisio Martín-Zanca², and Brian B. Rudkin¹

¹ Laboratoire de Biologie Moléculaire et Cellulaire, Unité Mixte de Recherche 49, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France, ² Instituto de Microbiología Bioquímica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, 37007 Salamanca, Spain, and ³ Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom

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 microscopic analysis of cell populations labeled with antibodies to the extracellular domains of both receptors. Differential expression of these receptors also was evidenced by biotinylation of surface proteins and Western analysis, using antibodies specific for the extracellular domains of TrkA and p75^NTR. TrkA is expressed most strongly at the cell surface in M and early G1 phases, whereas p75^NTR is expressed mainly in late G1, S, and G2 phases. This expression reflects the molecular 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., inhibition of the G1 to S transition, and the differentiation response whereas a survival effect is provoked elsewhere in the cell cycle. A model is proposed relating these responses to the surface expression of the two receptors. These observations open the way for novel approaches to the investigation of the mechanism of NGF signal transduction.

Key words: signaling; PC12 cells; TrkA antibodies; p75^NTR antibodies; flow cytometry; cell cycle; neurotrophin; receptor

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18176767-09$05.00/0

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