Role of GPI-anchored proteins in EphA3-induced retinal axon growth.

ORTALLI AL; ALVAREZ G; CARRI NG; TRUFFA A; PASQUALE EB; FLORES V; SCICOLONE G

Pinamar, Argentina.

Congreso; X Congress of the Panamerican Association for Biochemistry and Molecular Biology. XLI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology. XX Annual Meeting of the Argentine Society for Neurochemistry.; 2005

Panamerican Association for Biochemistry and Molecular Biology. Argentine Society for Biochemistry and Molecular Biology. Argentine Society for Neurochemistry.

ROLE OF GPI-ANCHORED PROTEINS IN EPHA3-INDUCED RETINAL AXON GROWTH. Ortalli, Ana L. 1; Alvarez, Gabriela1; Carri, Néstor G. 2; Truffa, Andrea1; Pasquale, Elena3; Sanchez, Viviana1; Flores, Vladimir1; Scicolone, Gabriel1. 1. I Biol Cel y Neuroc. FMED, UBA, Bs As, Argentina. 2. IMBICE, La Plata, Argentina. 3. Burnham Inst, La Jolla, USA. anaortalli@hotmail.com Nasal retinal ganglion cells connect to the caudal tectum and temporal ones contact the rostral tectum. Eph receptors and their ligands, the ephrins, are expressed in complementary gradients in both organs. EphrinAs located in caudal tectum repel EphA3-bearing temporal axons. Our results suggested that EphA3 in rostral tectum promote nasal axon growth to caudal tectum. As ephrinsA (GPI-anchored proteins) are expressed in optic fibers, we investigated if axonal GPI-anchored proteins mediate this effect. Retinal explants from 6 days-old chick embryos were cultured on EphA3-Fc or Fc. They were treated with increasing doses of PI-PLC, an enzyme that sheds GPI-anchored proteins. EphA3-Fc-stimulated nasal explants increase their axonal length at low PI-PLC doses, but reduce it at high PI-PLC doses. Control explants increase axonal length at every PI-PLC dose. Axonal density of nasal and temporal explants shows the same pattern of response as nasal axon length. The positive effect of PI-PLC treatment on control nasal axons suggests that endogenous ephrinAs could reduce axonal growth upon axonal EphA4 activation. The dual effect on EphA3-stimulated nasal axons also suggests that the lack of ephrinAs impairs EphA3-elicited axonal growth. It is possible that ephrinAs could act as receptors of EphA3. The weaker effect on temporal axons agrees with their lower expression of ephrinAs. This suggests that GPI-anchored proteins could participate in axonal guidance and ephrinAs could have a double role as both ligands and receptors. This work was supported by grants from CONICET and UBA. Argentina.