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

doi:10.1126/science.1100135

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: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

1015 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 language	English
Pages (from-to)	487-491
Journal	Science
Volume	306
Issue number	5695
DOIs	https://doi.org/10.1126/science.1100135
Publication status	Published - 15 Oct 2004
Externally published	Yes

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Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

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@article{7a2a4e0caf2e46afa49234fa8a698a5a,

title = "Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity",

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.",

author = "Pang, \{Petti T.\} and Teng, \{Henry K.\} and Eygene Zaitsev and Woo, \{Newton T.\} and Kazuko Sakata and Shushuang Zhen and Teng, \{Kenneth K.\} and Wing-Ho Yung and Hempstead, \{Barbara L.\} and Bai Lu",

note = "Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].",

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language = "English",

volume = "306",

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TY - JOUR

T1 - Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity

AU - Pang, Petti T.

AU - Teng, Henry K.

AU - Zaitsev, Eygene

AU - Woo, Newton T.

AU - Sakata, Kazuko

AU - Zhen, Shushuang

AU - Teng, Kenneth K.

AU - Yung, Wing-Ho

AU - Hempstead, Barbara L.

AU - Lu, Bai

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2004/10/15

Y1 - 2004/10/15

N2 - 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.

AB - 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.

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UR - https://app-overton-io.ezproxy.cityu.edu.hk/articles.php?query=10.1126/science.1100135

U2 - 10.1126/science.1100135

DO - 10.1126/science.1100135

M3 - RGC 21 - Publication in refereed journal

C2 - 15486301

SN - 0036-8075

VL - 306

SP - 487

EP - 491

JO - Science

JF - Science

IS - 5695

ER -

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

Abstract

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