NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis

Daniel J. Belliveau, Irena Krivko, Judi Kohn, Christian Lachance, Christine Pozniak, Dmitri Rusakov, David Kaplan, Freda D. Miller

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

161 Citas (Scopus)

Resumen

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 that activates TrkC, but not TrkA, is unable to support sympathetic neuron survival or neuritogenesis, indicating that NT-3-mediated TrkA activation is necessary for both of these responses. On the basis of these data, we suggest that NGF and NT-3 differentially regulate the TrkA receptor both with regard to activation time course and downstream targets, leading to selective regulation of neuritogenesis and survival. Such differential responsiveness to two ligands acting through the same Trk receptor has important implications for neurotrophin function throughout the nervous system.

Idioma originalEnglish
Páginas (desde-hasta)375-388
Número de páginas14
PublicaciónJournal of Cell Biology
Volumen136
N.º2
DOI
EstadoPublished - 1997
Publicado de forma externa

ASJC Scopus Subject Areas

  • Cell Biology

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

Huella

Profundice en los temas de investigación de 'NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis'. En conjunto forman una huella única.

Citar esto