Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 13, pp 1523-1537

First online:

Neurotrophin signaling: many exciting surprises!

  • J. C. ArévaloAffiliated withSkirball Institute of Biomolecular Medicine Lab 5-14, NYU School of Medicine Email author 
  • , S. H. WuAffiliated withSkirball Institute of Biomolecular Medicine Lab 5-14, NYU School of Medicine

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Neurotrophins are growth factors implicated in the development and maintenance of different neuronal populations in the nervous system. Neurotrophins bind to two sets of receptors, Trk receptor tyrosine kinases and the p75NTR receptor, to activate several different signaling pathways that mediate various biological functions. While Trk receptor activation has been well-studied and triggers the well-characterized Ras/Rap-MAPK, PI3K-Akt, and PLCγ-PKC cascades, p75NTR signaling is more complex, and its in vivo significance has not yet been completely determined. In the last few years, p75NTR has received much attention mainly due to recent findings describing pro-neurotrophins as new ligands for the receptor and the ability of the receptor to form different complexes with other transmembrane proteins. This review will update the neurotrophin signaling pathways known for Trk receptors to include newly identified Trk-interacting molecules and will address surprising new findings that suggest a role for p75NTR in different receptor complexes and functions.


Neurotrophin Trk p75NTR signaling neuron survival