IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SPROUTY4 IS A NEGATIVE MODULATOR OF TRKA SIGNALING AND NEURONAL DIFFERENTIATION INDUCED BY NGF
Autor/es:
ALSINA FC, IRALA D, FONTANET PA, HITA FJ, LEDDA F, PARATCHA G
Lugar:
Huerta Grande, Córdoba
Reunión:
Congreso; XXVI Congreso de la Sociedad Argentina de Neurociencias; 2011
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS (SAN)
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.