http://www.pnas.org/content/early/2012/09/07/1207767109.short
Abstract
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-p75NTR
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.
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