Research objectives and content
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin are two members of a growth factor family with potent neurotrophic activity for a wide range of neurons for the peripheral and central nervous system. Recently, it has been suggested that GDNFR-a, (a GPI-linked cell surface protein) and the Ret receptor tyrosine kinase (RTK), are two key components of the GDNF receptor complex. However, nothing is known about the receptor and signalling mechanism of Neurturin. We have identified two novel genes (called GDNFR-5 and GDNFR-Y) which appear to encode members of the GDNFR family of GPI- linked receptors. In this proposal, we wish to investigate the signalling specificity of GDNF and Neurturin in relation to the GDNFR molecules and the Ret RTK using Xenopus embryo and oocyte assays. In addition, in order to get insight into the in vivo function of the GDNFR-5 and GDNFR-y, genes, targeted inactivation experiments will be performed in mice.