Plasmin-mediated processing of protein tyrosine phosphatase receptor type Z in the mouse brain
Plasmin-mediated processing of protein tyrosine phosphatase receptor type Z in the mouse brain
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DOI：
10.1016/j.neulet.2008.07.028
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发表时间：
2008-09-19
影响因子：
2.5
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Chow, Jeremy Pak Hong;Fujikawa, Akihiro;Noda, Masaharu
蛋白酪氨酸磷酸酶受体Z型（Ptprz，也称为PTP zeta或RPTP β）优先在CNS中表达为主要的硫酸软骨素蛋白聚糖（CSPG）。Ptprz通过其在突触后密度中的细胞内羧基末端PDZ结合基序与PSD 95家族相互作用。ptprz缺陷的成年小鼠表现出空间和情境学习障碍。在这里，我们确定了Ptprz的蛋白水解处理纤溶酶在小鼠大脑中，这是显着增强后海人酸（KA）诱导的癫痫发作。我们映射纤溶酶裂解位点的Ptprz细胞外区域的细胞为基础的测定和重组蛋白的体外消化实验。这些发现表明Ptprz是tPA/纤溶酶系统活性依赖性蛋白水解加工的生理靶点，并表明蛋白水解切割参与学习和记忆过程中突触的功能过程。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTP zeta or RPTP beta) is preferentially expressed in the CNS as a major chondroitin sulfate proteoglycan (CSPG). Ptprz interacts with the PSD95 family through its intracellular carboxyl-terminal PDZ-binding motif in the postsynaptic density. Ptprz-deficient adult mice display impairments in spatial and contextual learning. Here, we identified the proteolytic processing of Ptprz by plasmin in the mouse brain, which is markedly enhanced after kainic acid (KA)-induced seizures. We mapped plasmin cleavage sites in the extracellular region of Ptprz by cell based assays and in vitro digestion experiments with recombinant proteins. These findings indicate that Ptprz is a physiological target for activity-dependent proteolytic processing by the tPA/plasmin system, and suggest that the proteolytic cleavage is involved in the functional processes of the synapses during learning and memory. (c) 2008 Elsevier Ireland Ltd. All rights reserved.