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BDNF sends mixed signals

Pro-BDNF causes presynaptic nerve cells (green) to retract from postsynaptic muscle cells (red).

Two different forms of the same protein have a "yin and yang" function to either promote or inhibit synaptic activity.

The nervous system modifies the strength of its connections in response to changes in synaptic activity—a process known as synaptic plasticity. One source of this plasticity is the postsynaptic cell, which sends a retrograde signal back across the synapse to either strengthen or weaken further transmissions. One such retrograde signal is brain-derived neurotrophic factor (BDNF), which promotes synaptic activity by binding to the TrkB receptor on presynaptic cells. But BDNF is also secreted in an uncleaved precursor form called pro-BDNF that binds to a different receptor called p75^NTR. Yang et al. wondered whether this form of the protein could have a different effect on synapses.

The team measured synaptic activity at neuromuscular junctions formed in vitro between Xenopus nerve and muscle cells. Adding a noncleavable version of pro-BDNF decreased activity at the synapses and caused nerve terminals to withdraw from the junctions. This behavior depended on p75^NTR, since knocking down the receptor in the presynaptic motor neurons prevented pro-BDNF's inhibitory effects.

Postsynaptic muscle cells could also secrete endogenous pro-BDNF to depress synaptic activity, the authors found, particularly if matrix metalloprotease (MMP) inhibitors were added to prevent the precursor from being processed to the mature form. This suggests that cleavage of pro-BDNF by MMPs is the key to switching the retrograde signal from depressing to potentiating synapses. Senior author Bai Lu now wants to study how the MMPs are regulated. He thinks that active presynaptic nerve cells secrete the enzymes into the synapse to cleave BDNF and strengthen the synaptic connection.

References

Yang, F., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200811147.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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Pro-BDNF–induced synaptic depression and retraction at developing neuromuscular synapses

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This Article Full Text (PDF, 489K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Short, B. Search for Related Content PubMed Articles by Short, B. Related Collections Related Article Social Bookmarking                            What's this?