PMID- 19451278 OWN - NLM STAT- MEDLINE DCOM- 20090622 LR - 20220309 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 185 IP - 4 DP - 2009 May 18 TI - Pro-BDNF-induced synaptic depression and retraction at developing neuromuscular synapses. PG - 727-41 LID - 10.1083/jcb.200811147 [doi] AB - Postsynaptic cells generate positive and negative signals that retrogradely modulate presynaptic function. At developing neuromuscular synapses, prolonged stimulation of muscle cells induces sustained synaptic depression. We provide evidence that pro-brain-derived neurotrophic factor (BDNF) is a negative retrograde signal that can be converted into a positive signal by metalloproteases at the synaptic junctions. Application of pro-BDNF induces a dramatic decrease in synaptic efficacy followed by a retraction of presynaptic terminals, and these effects are mediated by presynaptic pan-neurotrophin receptor p75 (p75(NTR)), the pro-BDNF receptor. A brief stimulation of myocytes expressing cleavable or uncleavable pro-BDNF elicits synaptic potentiation or depression, respectively. Extracellular application of metalloprotease inhibitors, which inhibits the cleavage of endogenous pro-BDNF, facilitates the muscle stimulation-induced synaptic depression. Inhibition of presynaptic p75(NTR) or postsynaptic BDNF expression also blocks the activity-dependent synaptic depression and retraction. These results support a model in which postsynaptic secretion of a single molecule, pro-BDNF, may stabilize or eliminate presynaptic terminals depending on its proteolytic conversion at the synapses. FAU - Yang, Feng AU - Yang F AD - Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Je, Hyun-Soo AU - Je HS FAU - Ji, Yuanyuan AU - Ji Y FAU - Nagappan, Guhan AU - Nagappan G FAU - Hempstead, Barbara AU - Hempstead B FAU - Lu, Bai AU - Lu B LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Precursors) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (brain-derived neurotrophic factor precursor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/*physiology MH - Muscle Cells/physiology MH - Neuromuscular Junction/*growth & development MH - Presynaptic Terminals/*ultrastructure MH - Protein Precursors/metabolism/*physiology MH - Receptor, Nerve Growth Factor/*physiology MH - Synapses MH - *Synaptic Transmission MH - Xenopus PMC - PMC2711569 EDAT- 2009/05/20 09:00 MHDA- 2009/06/23 09:00 PMCR- 2009/11/18 CRDT- 2009/05/20 09:00 PHST- 2009/05/20 09:00 [entrez] PHST- 2009/05/20 09:00 [pubmed] PHST- 2009/06/23 09:00 [medline] PHST- 2009/11/18 00:00 [pmc-release] AID - jcb.200811147 [pii] AID - 200811147 [pii] AID - 10.1083/jcb.200811147 [doi] PST - ppublish SO - J Cell Biol. 2009 May 18;185(4):727-41. doi: 10.1083/jcb.200811147.