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用N-Terminomics识别Calpain-5的蛋白质溶解基质的鉴定

Jozsef Gal^1,2,3,4, Antoine Dufour^5,6, Daniel Young^5,6

¹Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, KY 40536, USA.

International journal of molecular sciences

|July 12, 2025

概括

使用N-terminomics研究了calpain-5 (CAPN5) 蛋白酶活性. 研究人员确定了新的CAPN5基质,包括与神经退行和突触功能相关的蛋白质,揭示了其生物作用的新见解.

科学领域:

生物化学生物化学
蛋白质组学是指蛋白质组学.
神经科学是一个神经科学.

背景情况:

卡尔-5 (CAPN5) 是一种激活的囊蛋白酶,其基质谱未知.
卡尔帕因通过裂解内部蛋白质残留物产生新N-终端.
了解CAPN5基质对于阐明其功能和相关疾病至关重要.

研究的目的:

通过定量N-terminomics方法识别Calpain-5 (CAPN5) 的基质.
描述神经元细胞中CAPN5的蛋白质分解活性.
探索CAPN5基质在神经退行症和新血管炎症性玻璃色素病变 (NIV) 中的影响.

主要方法:

使用了TAILS (基质的终端氨基同位素标记) N-terminomics技术.
在父母细胞中的N终端与缺乏CAPN5的SH-SY5Y神经母细胞瘤细胞进行比较.
使用共免疫沉,体外蛋白质溶解试验和细胞碎片化分析验证的基质候选物.

主要成果:

鉴定了30个新N终端,对应于24个独特的蛋白质,在CAPN5缺乏细胞中耗尽.
提供了CAPN5介导的突触蛋白 (DLGAP4,IQSEC1,MPDZ),神经退行相关蛋白 (EWS,hNRNPU,TFG,UGP2),MCM3和LMTK1.1) 的裂变的证据.
数据通过ProteomeXchange (标识符PXD064313) 提供给公众.

结论:

建立了CAPN5基质的目录,扩大了对其蛋白质分解标的理解.
突出了CAPN5在分裂涉及突触功能,神经退行,DNA复制和神经元分化中的蛋白质中的作用.
将CAPN5活动与新血管炎症性玻璃红蛋白病变 (NIV) 联系在一起,这表明CAPN5中的病原性突变与这种渐进性眼睛疾病有关.

关键词:

在CAPN5中使用CAPN5.在N-terminomics中,我们可以使用N-terminomics.尾巴尾巴是一种尾巴.疾病疾病疾病疾病蛋白质酶蛋白质酶是一种蛋白质.

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