IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Wingless-type family member 3A (Wnt3a) triggers polarization of hippocampal neurons via cross-activation of the IGF-1 receptor/PI3k pathway.
Autor/es:
BERNIS ME; DUPRAZ S; OKSDATH M; FERNÁNDEZ M ; MALCHIODI E; ROSSO S ; QUIROGA S
Revista:
Front Cell Neurosci
Editorial:
Frontiers Research Foundation
Referencias:
Lugar: Lausanne; Año: 2013 vol. 7 p. 1 - 12
Resumen:
Initial axonal elongation is essential for neuronal polarization and
requires polarized activation of IGF-1 receptors (IGF-1r) and the
phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family
growth factors (Wnts) have also been implied in the regulation of axonal
development. It is not known, however, if Wnts have any participation
in the regulation of initial axonal outgrowth and the establishment of
neuronal polarity. We used cultured hippocampal neurons and growth cone
particles (GCPs) isolated from fetal rat brain to show that stimulation
with the wingless family factor 3A (Wnt3a) was sufficient to promote
neuronal polarization in the absence of IGF-1 or high insulin. We also
show that Wnt3a triggered a strong activation of IGF-1r, PI3k, and Akt
in developmental Stage 2 neurons and that the presence of activatable
IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects.
Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind
specifically to the IGF-1r. Using crosslinking and immuno-precipitation
experiments, we show that stimulation with Wnt3a triggered the
formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude
that Wnt3a triggers polarization of neurons via cross-activation of the
IGF-1r/PI3k pathway upon binding to Fz7.