Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity

Petti T. Pang, Henry K. Teng, Eygene Zaitsev, Newton T. Woo, Kazuko Sakata, Shushuang Zhen, Kenneth K. Teng, Wing Ho Yung, Barbara L. Hempstead, Bai Lu

Research output: Contribution to journalArticle

771 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalScience
Volume306
Issue number5695
DOIs
StatePublished - Oct 15 2004
Externally publishedYes

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Long-Term Potentiation
Fibrinolysin
Brain-Derived Neurotrophic Factor
Tissue Plasminogen Activator
Proteins
Long-Term Memory
Hippocampus
Peptide Hydrolases

All Science Journal Classification (ASJC) codes

  • General

Cite this

Pang, P. T., Teng, H. K., Zaitsev, E., Woo, N. T., Sakata, K., Zhen, S., ... Lu, B. (2004). Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science, 306(5695), 487-491. https://doi.org/10.1126/science.1100135

Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. / Pang, Petti T.; Teng, Henry K.; Zaitsev, Eygene; Woo, Newton T.; Sakata, Kazuko; Zhen, Shushuang; Teng, Kenneth K.; Yung, Wing Ho; Hempstead, Barbara L.; Lu, Bai.

In: Science, Vol. 306, No. 5695, 15.10.2004, p. 487-491.

Research output: Contribution to journalArticle

Pang, PT, Teng, HK, Zaitsev, E, Woo, NT, Sakata, K, Zhen, S, Teng, KK, Yung, WH, Hempstead, BL & Lu, B 2004, 'Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity', Science, vol. 306, no. 5695, pp. 487-491. https://doi.org/10.1126/science.1100135
Pang, Petti T. ; Teng, Henry K. ; Zaitsev, Eygene ; Woo, Newton T. ; Sakata, Kazuko ; Zhen, Shushuang ; Teng, Kenneth K. ; Yung, Wing Ho ; Hempstead, Barbara L. ; Lu, Bai. / Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. In: Science. 2004 ; Vol. 306, No. 5695. pp. 487-491.
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