Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen
Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen
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DOI：
10.1016/s0304-4165(02)00256-8
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发表时间：
2002-07-03
影响因子：
3
通讯作者：
Kaplan, A
中科院分区：
文献类型：
--
作者：
Das, A;Smalheiser, NR;Kaplan, A
为了鉴定与人淀粉样前体蛋白 (APP) N 端部分结合的配体，我们寻找人 APP695 胞外域片段 (sAPP(T-695)) 的结合伴侣。探针在体外与大鼠皮质膜制剂中的高分子量激肽原 (HK) 片段结合。激光共聚焦显微镜表明 APP 和 HK 在脑血管附近、神经纤维和大鼠大脑的许多神经元中共定位。 sAPP(695)T 与人活化激肽原 (HKa) 结合 (K-d = 0.3 +/- 0.1 nM)，但与失活或低分子量激肽原不结合。生物素化人 HKa 的轻链序列也与 sAPP(695) 结合 (K-d = 0.3 +/- 0.5 nM) 和 HKa 形成紧密结合。这些结果支持了 APP 和激肽原可以在脑组织中相互作用的假设，考虑到 APP 对神经突生长的影响，APP-HKa 相互作用可以调节神经发生。 (C) 2002 Elsevier Science B.V. 保留所有权利。
To identify ligands that bind to the N-terminal portion of human amyloid precursor protein (APP), we sought binding partners for a fragment of the ectodomain of human APP695 (sAPP(T-695). The probe bound to fragments of high molecular weight kininogen (HK) in rat cortical membrane preparations in vitro. Laser confocal microscopy indicated that APP and HK colocalize near cerebral blood vessels, in the neuropil, and in many neurons of rat brain. sAPP(695)T bound to human activated kininogen (HKa) (K-d = 0.3 +/- 0.1 nM), but not to inactivated or low molecular weight kininogen. Binding was specific for the light chain sequence of HKa. Biotinylated human HKa also bound to sAPP(695) (K-d = 0.3 +/- 0.5 nM). sAPP(695) and HKa form tight complexes in solution that can be coimmunoprecipitated. These results support the hypothesis that forms of APP and kininogen can interact in brain tissue. Considering the implications of APP in neurite outgrowth, the APP-HKa interaction could modulate neurogenesis. (C) 2002 Elsevier Science B.V. All rights reserved.