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Science 15 October 2004:
Vol. 306. no. 5695, pp. 487 - 491
DOI: 10.1126/science.1100135
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Reports

Cleavage of proBDNF by tPA/Plasmin Is Essential for Long-Term Hippocampal Plasticity

Petti T. Pang,1,3 Henry K. Teng,2 Eugene Zaitsev,1 Newton T. Woo,1 Kazuko Sakata,1 Shushuang Zhen,2 Kenneth K. Teng,2 Wing-Ho Yung,3 Barbara L. Hempstead,2 Bai Lu1*

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.

1 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.
2 Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
3 Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

* To whom correspondence should be addressed. E-mail: bailu{at}mail.nih.gov

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