Neurturin, a relative of glial-cell-line-derived neurotrophic factor.
The normal development of the vertebrate nervous system entails the death of 30-70% of the neurons originally generated in most neuronal populations. This naturally occurring cell death is regulated by specific neurotrophic factors that promote neuronal survival and which are produced in limiting quantities by target cells, glial cells and neurons. These factors are also of potential utility as therapeutic agents for neurodegenerative diseases. Here we describe the purification and cloning of a new neurotrophic factor, identified on the basis of its ability to support the survival of sympathetic neurons in culture. This factor, neurturin, is structurally related to glial-cell-line-derived neurotrophic factor (GDNF). These factors can each activate the MAP kinase signalling pathway in cultured sympathetic neurons and support the survival of sympathetic neurons, as well as of sensory neurons of the nodose and dorsal root ganglia. Thus, neurturin and GDNF together now define a new family of neurotrophic factors.
Kotzbauer
P T
PT
Division of Laboratory Medicine, Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Lampe
P A
PA
Heuckeroth
R O
RO
Golden
J P
JP
Creedon
D J
DJ
Johnson
E M
EM
Milbrandt
J
J
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D006224:Cricetinae; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051101:Neurturin; D009620:Nodose Ganglion / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D017783:Superior Cervical Ganglion / Q000166:cytology
D017077:Culture Media, Conditioned; D018076:DNA, Complementary; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; C495057:Nrtn protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases