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Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses

Je, H. Shawn ; Yang, Feng ; Ji, Yuanyuan ; Nagappan, Guhan ; Hempstead, Barbara L ; Lu, Bai

Proceedings of the National Academy of Sciences - PNAS, 2012-09, Vol.109 (39), p.15924-15929 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses
Autor: Je, H. Shawn ; Yang, Feng ; Ji, Yuanyuan ; Nagappan, Guhan ; Hempstead, Barbara L ; Lu, Bai
Assuntos: Animal cognition ; Animals ; Axons ; Biological Sciences ; Brain ; Brain-Derived Neurotrophic Factor - genetics ; Brain-Derived Neurotrophic Factor - metabolism ; Cells, Cultured ; coculture ; Coculture Techniques ; Fluorescence ; Frogs ; Innervation ; Molecular structure ; motor neurons ; Motor Neurons - cytology ; Motor Neurons - metabolism ; Muscle cells ; Muscle Fibers, Skeletal - cytology ; Muscle Fibers, Skeletal - metabolism ; nerve tissue ; Neuromuscular Junction - genetics ; Neuromuscular Junction - metabolism ; Neurons ; Neuroscience ; Protease inhibitors ; Protein Precursors - genetics ; Protein Precursors - metabolism ; proteolysis ; Receptor, trkB - genetics ; Receptor, trkB - metabolism ; Receptors, Nerve Growth Factor - genetics ; Receptors, Nerve Growth Factor - metabolism ; Secretion ; Signal transduction ; Signal Transduction - physiology ; synapse ; Synapses ; Xenopus ; Xenopus laevis ; Xenopus Proteins - genetics ; Xenopus Proteins - metabolism
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2012-09, Vol.109 (39), p.15924-15929
Notas: http://dx.doi.org/10.1073/pnas.1207767109
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1H.S.J. and F.Y. contributed equally to this work.
Author contributions: H.S.J., F.Y., and B.L. designed research; H.S.J., F.Y., Y.J., and G.N. performed research; B.L.H. contributed new reagents/analytic tools; H.S.J., F.Y., and Y.J. analyzed data; and H.S.J., F.Y., and B.L. wrote the paper.
Edited* by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved August 20, 2012 (received for review May 10, 2012)
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses

Je, H. Shawn ; Yang, Feng ; Ji, Yuanyuan ; Nagappan, Guhan ; Hempstead, Barbara L ; Lu, Bai

United States: National Academy of Sciences

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