Neurotrophins: structural relatedness and receptor interactions.
Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are structurally related proteins that allow the survival of specific populations of embryonic vertebrate neurons. The primary structure of these neurotrophins, deduced from their nucleotide sequences, indicates that all three are synthesized in the form of precursor proteins presumably allowing for appropriate folding, including the formation of disulphide bridges, cleavage and secretion. While no information is yet available on the 3-dimensional structures of the neurotrophins, results from binding studies using the three neurotrophins as ligands indicate that their receptors do recognize similarities, as well as differences, between them. High-affinity receptors, that presumably mediate the biological response, as well as low-affinity receptors are present on neurons responsive to the neurotrophins. Whereas a large excess of heterologous ligand is needed to reduce binding of a particular neurotrophin to its high-affinity receptor, the same concentration of homologous or heterologous ligand similarly reduce the binding of any of the three neurotrophins to the low-affinity receptor. For all three, the low-affinity receptor appears to be the already characterized NGF low-affinity receptor that seems to be an integral part of the high-affinity receptor complexes. These results suggest that the regulation of neuronal survival by target cells can, in part, be explained by the release from these cells of limiting quantities of the structurally related neurotrophins, each being recognized by a specific high-affinity receptor complex located on the nerve terminals of the responsive neurons.
Rodríguez-Tébar
A
A
Cajal Institute of Neurobiology, Madrid, Spain.
Dechant
G
G
Barde
Y A
YA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D015394:Molecular Structure; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D020933:Neurotrophin 3; D011956:Receptors, Cell Surface / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor