The G-protein inhibitor, pertussis toxin, inhibits the secretion of brain-derived neurotrophic factor
| Autor: | James E. Johnson, Mark Bothwell, C.S. von Bartheld, L.J Goodman, E.C Gunther |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Biological Transport Active Chick Embryo GTP-Binding Protein alpha Subunits Gi-Go Ciliary neurotrophic factor Pertussis toxin Retina Cell Line Potassium Chloride Mice GTP-Binding Proteins Neurotrophic factors Internal medicine Glial cell line-derived neurotrophic factor medicine Animals Humans Tissue Distribution Visual Pathways Secretion Virulence Factors Bordetella Neurons Brain-derived neurotrophic factor Cell Death biology Brain-Derived Neurotrophic Factor General Neuroscience Osmolar Concentration Heterotrimeric GTP-Binding Proteins Cell biology Endocrinology Pertussis Toxin biology.protein Neurotrophin |
| Zdroj: | Neuroscience. 100:569-579 |
| ISSN: | 0306-4522 |
| Popis: | Secretion of neurotrophins is critical for the delivery of neurotrophic support. Brain-derived neurotrophic factor is targeted to a regulated secretory pathway in neurons as well as the neurosecretory AtT-20 cells. Here, we show that pertussis toxin, which inactivates Gi and Go G proteins, inhibits up to 50% of the regulated release of brain derived neurotrophic factor by AtT-20 cells. To determine whether pertussis toxin-sensitive G proteins may regulate brain-derived neurotrophic factor release in vivo, the effect of intraocular pertussis toxin was assessed on the isthmo-optic nucleus in the developing chick visual system. The isthmo-optic nucleus projects axons from the midbrain to innervate retinal amacrine cells and depends on target-derived brain-derived neurotrophic factor between embryonic days 13 and 17 (E13-17). During this period approximately 50% of isthmo-optic neurons are eliminated by programmed cell death. Intraocular pertussis toxin administered at E13 increased cell death of isthmo-optic neurons by 42%, whereas injections at E19 had no effect. Co-injection of brain-derived neurotrophic factor with pertussis toxin rescued approximately 50% of isthmo-optic neurons from enhanced cell death, although overall retinal brain derived neurotrophic factor protein levels were unaffected by pertussis toxin. Retrograde transport of exogenous 125I-labeled brain derived neurotrophic factor from the retina to the midbrain was increased by co-administration of pertussis toxin, possibly owing to diminished competition from endogenously released brain-derived neurotrophic factors for the receptors that mediate retrograde axonal transport. These data suggest that the release of a major fraction of brain-derived neurotrophic factor in the secretory pathway in vitro and in vivo is regulated by the activity of pertussis toxin-sensitive G proteins. |
| Databáze: | OpenAIRE |
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