标题:Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain.
期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1990
卷号:87
期号:14
页码:5454-5458
DOI:10.1073/pnas.87.14.5454
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:We have used a pool of degenerate oligonucleotides representing all possible codons in regions of homology between brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) to prime rat hippocampal cDNAs in the polymerase chain reaction. The amplified DNA included a product with significant similarity to NGF and BDNF, which was used to isolate a 1020-nucleotide-long cDNA from a rat hippocampal library. From the nucleotide sequence, a 282-amino-acid-long protein with approximately 45% amino acid similarity to both pig BDNF and rat NGF was deduced. In the adult brain, the mRNA for this protein was predominantly expressed in hippocampus, where it was confined to a subset of pyramidal and granular neurons. The developmental expression in brain showed a clear peak shortly after birth, 1 and 2 weeks earlier than maximal expression of BDNF and NGF, respectively. It was also expressed in several peripheral tissues with the highest level in kidney. The protein, transiently expressed in COS cells, was tested on chicken embryonic neurons and readily stimulated fiber outgrowth from explanted Remak's ganglion and, to a lesser extent, the nodose ganglion. A weak, but consistent, fiber outgrowth response was also seen in the ciliary ganglion and in paravertebral sympathetic ganglia. Moreover, the protein displaced binding of NGF to its receptor, suggesting that it can interact with the NGF receptor. Thus, this factor, although structurally and functionally related to NGF and BDNF, has unique biological activities and represents a member of a family of neurotrophic factors that may cooperate to support the development and maintenance of the vertebrate nervous system.