p135 is a novel signaling receptor for GDNF-family ligands

PARATCHA, G; LEDDA, F; IBANEZ CF

Newport (Rodhe Island) USA

Conferencia; Gordon Research Conferences of Neurotrophins.; 2001

Gordon Research Conferences

Intercellular communication involves either direct cell-cell contact or release and uptake of diffusible signals, two strategies mediated by distinct and largely nonoverlapping sets of molecules. Here, we show that p135 Kd protein can function as a signaling receptor for members of the GDNF ligand family. Association of p135 with GFRalpha1, a GPI-anchored receptor for GDNF promotes high-affinity binding of GDNF to p135, resulting in rapid activation of cytoplasmic protein tyrosine kinases Fyn and FAK in cells lacking RET, a known GDNF signaling receptor. GDNF stimulates Schwann cell migration and axonal growth in hippocampal and cortical neurons via binding to p135 and activation of Fyn, but independently of RET. These results reveal a novel pathway for GDNF signaling that does not require the RET receptor.