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XB-ART-39972
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 .


Abstract
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