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

作者：Petti T. Pang, Henry K. Teng, Eugene N. Zaitsev, Newton T. Woo, Kazuko Sakata, Shushuang Zhen, Kenneth K. Teng, Wing‐Ho Yung, Barbara L. Hempstead, Bai Lu · 发表于：Science · 年份：2004 · DOI：10.1126/science.1100135 · 被引用次数：1141 · 研究领域：Nerve injury and regeneration、Calpain Protease Function and Regulation、Neurogenesis and neuroplasticity mechanisms

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.