EphA4 vs EphA3: fight for the ephrin-As

FIORE, LUCIANO; DI NAPOLI, JENNIFER; BENÍTEZ, ROCÍO; RAPACIOLI MELINA; CARRI, NESTOR G; SCICOLONE, GABRIEL

Huerta Grande, Córdoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2011

Sociedad Argentina de Investigación en Neurociencia.

EphA4 vs EphA3: fight for the ephrin-AsContenido:Ephrin-As of the caudal tectum repel temporal (T) axons of retinal ganglion cells (RCG) by activating EphAs. We established that EphA3 stimulates nasal (N) RGCs axon growth to caudal tectum and inhibits branching rostrally to their target area. Our aim was to study the molecular way of action of EphA3. We used retinal explants from chicken embryos treated with EphA3Fc/Fc, PIPLC (sheds ephrin-As) or KYL (inhibits ephrin-A-mediated EphA4 activation). We performed immunocytochemistry, immunoprecipitation and Western blot. NRGCs present higher levels of ephrin-As and EphA4ptyr602. Ephrin-As and EphA4 coexpress mainly in NRGCs. As TRGCs grow longer axons and present less filopodia and NRGCs present the higher respond to EphA3Fc, it was suggested that ephrin-As-mediated EphA4 forward signaling decreases axon growth and stimulates branching whereas the opposite effects produced by EphA3 are mediated by decreasing EphA4 signaling throughout competition of EphAs binding to ephrin-As. We showed that removing axonal ephrin-As or inhibiting EphA4 activation reproduces the effects of EphA3.These results support a novel mechanism of action of EphA3 whereby plays their roles by diminishing the ephrin-As-mediated EphA4 forward signaling. Founded by UBA-CONICET.