BECAS
HITA Francisco Javier
congresos y reuniones científicas
Título:
Sprouty4 is a negative modulator of TrkA signaling and neuronal differentiation induced by NGF
Autor/es:
ALSINA, FERNANDO C.; IRALA, DOLORES; FONTANET, PAULA A.; HITA, FRANCISCO J.; LEDDA, FERNANDA; PARATCHA, GUSTAVO C.
Reunión:
Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011
Resumen:
The Sprouty (Spry) family of proteins represents endogenous
regulators of downstream signaling pathways induced by receptor tyrosine
kinases (RTKs). Despite of the essential contribution of nerve growth factor
(NGF) for neuronal development and function, the molecular mechanisms that
control NGF-induced TrkA signaling are not totally understood. Using a cDNA
microarray screening, we identify Spry4 as a potential modulator of
intracellular signaling pathways and biological processes induced by NGF and
its receptor TrkA. qRT-PCR assays confirme that Spry4, but not Spry1-2, is
significantly induced by NGF in PC12 and primary dorsal root ganglia (DRG)
neurons. Ectopic expression of wt Spry4 causes a significant reduction in MAPK
and Rac1 activation and neurite outgrowth induced by NGF. Ectopic expression of
a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was
replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite
outgrowth induced by NGF, suggesting that an intact Tyr 53 site is required for
the inhibitory effect of Spry4 on NGF signaling. Together, these findings
establish a new physiological mechanism through which Spry4 regulates neurite
outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation
in response to NGF.