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J Cell Biol 2009 May 18;1854:727-41. doi: 10.1083/jcb.200811147.
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Pro-BDNF-induced synaptic depression and retraction at developing neuromuscular synapses.

Yang F , Je HS , Ji Y , Nagappan G , Hempstead B , Lu B .

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.

PubMed ID: 19451278
PMC ID: PMC2711569
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: bdnf mmp3 ngfr
Morpholinos: bdnf MO1 ngfr MO2

Article Images: [+] show captions
References [+] :
Balice-Gordon, Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions. 1993, Pubmed