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Neurotrophin receptor structure and interactions.

H Yano1, M V Chao

  • 1Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, NY 10016, USA.

Pharmaceutica Acta Helvetiae
|May 17, 2000
PubMed
Summary

Biological responses often involve multiple receptor systems, not just single receptors. Neurotrophin receptors, like NGF, can signal for cell survival or death through complex interactions.

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Area of Science:

  • Cellular and Molecular Biology
  • Neuroscience
  • Signal Transduction

Background:

  • Receptor signaling traditionally viewed as linear, but trans-signaling via multiple receptor systems is increasingly recognized.
  • Trophic factors like nerve growth factor (NGF) mediate neuronal survival through complex pathways involving receptor tyrosine kinases and phosphatidylinositol-3-kinase.
  • NGF receptors (TrkA and p75) exemplify bidirectional crosstalk, influencing cell survival, differentiation, or apoptosis.

Purpose of the Study:

  • To explore the mechanisms of receptor trans-signaling and crosstalk in biological responses.
  • To elucidate the dual role of neurotrophin receptors in promoting neuronal survival and apoptosis.
  • To highlight the complexity beyond linear receptor signaling models.

Main Methods:

  • Review of established mechanisms in growth factor and trophic factor signaling.
  • Analysis of signaling pathways activated by NGF family neurotrophins, including TrkA, Akt/PKB, and p75.
  • Examination of receptor interactions and their downstream effects, such as NF-kappa B induction and sphingomyelin hydrolysis.

Main Results:

  • Biological responses are frequently mediated by trans-signaling involving multiple receptor systems.
  • NGF signaling activates both ras-dependent and ras-independent pathways for neuronal survival.
  • The p75 receptor, in conjunction with TrkA, can promote survival or, independently, induce apoptosis via ceramide production.

Conclusions:

  • Receptor crosstalk and trans-signaling provide greater flexibility in biological responses.
  • Neurotrophin receptors exhibit a bidirectional signaling capacity, crucial for neuronal development and potentially implicated in neurodegenerative diseases.
  • Understanding these complex receptor interactions is critical for deciphering cellular signaling.

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