Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity.
Long-term memory is thought to be mediated by protein synthesis-dependent, late-phase long-term potentiation (L-LTP). Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their relationship is unclear. Here we report that tPA, by activating the extracellular protease plasmin, converts the precursor proBDNF to the mature BDNF (mBDNF), and that such conversion is critical for L-LTP expression in mouse hippocampus. Moreover, application of mBDNF is sufficient to rescue L-LTP when protein synthesis is inhibited, which suggests that mBDNF is a key protein synthesis product for L-LTP expression.
Section on Neural Development and Plasticity, Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development (NICHD), Bethesda, MD 20892, USA.
Petti T
PT
Pang
Henry K
HK
Teng
Eugene
E
Zaitsev
Newton T
NT
Woo
Kazuko
K
Sakata
Shushuang
S
Zhen
Kenneth K
KK
Teng
Wing-Ho
WH
Yung
Barbara L
BL
Hempstead
Bai
B
Lu
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005341:Fibrinolysin / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011233:Precipitin Tests; D011498:Protein Precursors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin