title: Motoneuron programmed cell death in response to proBDNF.
abstract: Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75(NTR) and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75(NTR) and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Taylor
authors.forename: David J
authors.initials: DJ
authors.lastname: Gifondorwa
authors.forename: Mac B
authors.initials: MB
authors.lastname: Robinson
authors.forename: Jane L
authors.initials: JL
authors.lastname: Strupe
authors.forename: David
authors.initials: D
authors.lastname: Prevette
authors.forename: James E
authors.initials: JE
authors.lastname: Johnson
authors.forename: Barbara
authors.initials: B
authors.lastname: Hempstead
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Oppenheim
authors.forename: Carolanne E
authors.initials: CE
authors.lastname: Milligan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000294:innervation / Q000378:metabolism; D061251:Primary Cell Culture; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D019208:Brain-Derived Neurotrophic Factor; D053148:Caspase 3; D053179:Caspase 7; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; D000099183:Sortilin; C426674:brain-derived neurotrophic factor precursor