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Sequential transport from early to late endosomes requires the coordinated activities of the small GTPases Rab5 and Rab7. The transition between early and late endosomes could be mediated either through transport carriers or by Rab conversion, a process in which the loss of Rab5 from an endosome occurs concomitantly to the acquisition of Rab7. We demonstrate that Rab conversion is the mechanism by...
The glial cell-derived neurotrophic factor (GDNF) precursor contains several putative sites for prohormone convertase-mediated excision of short peptides. Here, we show that one of the predicted peptides, named BEP (brain excitatory peptide), induces a substantial increase in the synaptic excitability in rat CA1 pyramidal neurons. The excitation is sensitive to N-ethylmaleimide, suggesting involvement...
Glial cell line-derived neurotrophic factor (GDNF) has potentially great clinical importance in the treatment of Parkinson's disease and several other neurodegenerative diseases, however its intracellular signaling mechanisms are poorly understood. Here we show that upon GDNF binding glycosyl-phosphatidylinositol (GPI)-linked GDNF receptor α1 (GFRα1) activates cytoplasmic Src family tyrosine kinase(s)...
Glial cell line–derived neurotrophic factor (GDNF) and a related protein, neurturin (NTN), require a GPI-linked coreceptor, either GFRα1 or GFRα2, for signaling via the transmembrane Ret tyrosine kinase. We show that mice lacking functional GFRα2 coreceptor (Gfra2−/−) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation...
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