title: Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses.
abstract: Formation of specific neuronal connections often involves competition between adjacent axons, leading to stabilization of the active terminal, while retraction of the less active ones. The underlying molecular mechanisms remain unknown. We show that activity-dependent conversion of pro-brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF mediates synaptic competition. Stimulation of motoneurons triggers proteolytic conversion of proBDNF to mBDNF at nerve terminals. In Xenopus nerve-muscle cocultures, in which two motoneurons innervate one myocyte, proBDNF-p75(NTR) signaling promotes retraction of the less active terminal, whereas mBDNF-tyrosine-related kinase B (TrkB) p75NTR (p75 neurotrophin receptor) facilitates stabilization of the active one. Thus, proBDNF and mBDNF may serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBDNF may regulate synapse elimination.
authors.affiliation: Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, MD 20892-3714, USA.
authors.forename: H Shawn
authors.initials: HS
authors.lastname: Je
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Guhan
authors.initials: G
authors.lastname: Nagappan
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Hempstead
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; D029867:Xenopus Proteins; D020813:Receptor, trkB