Functional cooperation between TrkA and p75NTR accelerates neuronal differentiation by increased transcription of GAP-43 and p21(CIP/WAF) genes via ERK1/2 and AP-1 activities

Daniel Diolaiti, Roberto Bernardoni, Stefania Trazzi, Antonella Papa, Antonio Porro, Françoise Bono, Jean Marc Herbert, Giovanni Perini, Giuliano Della Valle

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29 Citations (Scopus)


The biological complexity of NGF action is achieved by binding two distinct neurotrophin receptors, TrkA and p75NTR. While several reports have provided lines of evidence on the interaction between TrkA and p75NTR at the plasma membrane, much fewer data are available on the consequence of such an interaction in terms of intracellular signaling. In this study, we have focused on how p75NTR may affect TrkA downstream signaling with respect to neuronal differentiation. Here, we have shown that cooperation between p75NTR and TrkA results in an increased NGF-mediated TrkA autophosphorylation, leads to a sustained activation of ERK1/2 and accelerates neurite outgrowth. Interestingly, neurite outgrowth is concomitant with a selective enhancement of the AP-1 activity and the transcriptional activation of genes such as GAP-43 and p21(CIP/WAF), known to be involved in the differentiation process. Collectively, our results unveil a functional link between the specific expression profile of neurotrophin receptors in neuronal cells and the NGF-mediated regulation of the differentiation process possibly through a persistent ERKs activation and the selective control of the AP-1 activity.

Original languageEnglish
Pages (from-to)2980-2992
Number of pages13
JournalExperimental Cell Research
Issue number14
Publication statusPublished - 15 Aug 2007
Externally publishedYes


  • AP-1 GAP-43
  • ERK1/2
  • NGF
  • p21(CIP/WAF)
  • p75
  • TrkA

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