Expression of TrkA confers neuron-like responsiveness to nerve growth factor on an immortalized hypothalamic cell line.
The result of nerve growth factor (NGF) actions depends upon the cells in which it signals. To define how signaling is influenced by cellular context, it would be useful to examine cells committed to different fates or cells of a single type at different developmental stages. Interest in NGF actions on neurons of the central nervous system led us to examine GT1-1 cells, an immortalized hypothalamic cell line. GT1-1 cells demonstrated neuronal properties but were unresponsive to NGF and other neurotrophins. Through transfection, trkA expression conferred NGF signaling leading to enhanced neuronal differentiation, including dose-dependent induction of neurite outgrowth and a rapid transient increase in c-fos and NGFI-A mRNA. Under serum-free culture conditions, NGF also delayed cell death. These findings suggest that trkA transfection of neurons and neuronal precursors can be used to better define NGF signaling.
Zhou
J
J
Department of Neurology, University of California, San Francisco 94143.
Holtzman
D M
DM
Weiner
R I
RI
Mobley
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003432:Cross-Linking Reagents; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D014162:Transfection
D003432:Cross-Linking Reagents; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA