Nerve growth factor (NGF) exerts its pro‐apoptotic effect via the P75NTR receptor in a cell cycle‐dependent manner

FEBS Letters

Bono, Françoise²  Savi, P.²  Bornia, Josette²  Della Valle, Giuliano¹  Lamarche, Isabelle²  Herbert, Jean-Marc² 

[1] Department of Biology, University of Bologna, Bologna, Italy;Haemobiology Research Department, Sanofi Recherche, 195 route d'Espagne, 31036 Toulouse, France

关键词: Neuroblastoma cell;    Apoptosis;    P75NTR;    TrkA;    Nerve growth factor;   

DOI  :  10.1016/S0014-5793(99)01006-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Nerve growth factor (NGF), the prototypic member of the neurotrophin family of growth factors, exerts its action via two receptors, P75^NTR and TrkA, the expression of which varies at the cell surface of neuroblastoma cells (SH-SY5Y cells) in a cycle phase-specific manner. NGF was pro-apoptotic on growing cells expressing preferentially P75^NTR and exhibited a potent anti-apoptotic effect on quiescent cells, when TrkA was prevalent at the cell surface, showing that NGF can have a dual action on SH-SY5Y cells depending on the relative cell surface expression of TrkA and P75^NTR. The pro-apoptotic activity of NGF but not its anti-apoptotic activity was abrogated by an antibody against the extracellular domain of P75^NTR and in cells isolated from P75^NTR knock-out mice indicating that NGF exhibits a pro-apoptotic activity via P75^NTR exclusively. On the other hand, we showed that the anti-apoptotic activity of NGF was specifically mediated by an interaction with TrkA with no contribution of P75^NTR, as demonstrated on SK-N-BE cells transfected with TrkA in which NGF was a potent anti-apoptotic compound but did not exhibit any pro-apoptotic activity. These results support the hypothesis that the survival response to NGF depends on its binding to TrkA without any involvement of P75^NTR which in turn selectively mediates the pro-apoptotic activity of NGF with no contribution of TrkA and show that, depending on the growth state of the cells, NGF exhibits dual pro- or anti-apoptotic properties via P75^NTR and TrkA, respectively.

【 授权许可】

Unknown