Comprehensive Analysis of Proteasomal Complexes in Mouse Brain Regions Detects ENO2 as a Potential Partner of the Proteasome in the Striatum.
Comprehensive Analysis of Proteasomal Complexes in Mouse Brain Regions Detects ENO2 as a Potential Partner of the Proteasome in the Striatum.
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DOI：
10.1007/s10571-021-01106-2
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发表时间：
2022-10
影响因子：
4
通讯作者：
Rezvani K
中科院分区：
文献类型：
--
作者：
Esfahanian N;Nelson M;Autenried R;Pattison JS;Callegari E;Rezvani K
蛋白酶体或其调节器的活性缺陷与几种病理有关，包括神经退行性疾病。我们假设，蛋白酶体的异质性及其选择性伙伴在不同的大脑区域会有所不同，并对蛋白酶体的催化活性产生重大影响。使用神经细胞培养和从小鼠获得的脑组织，我们比较了受神经退行性疾病影响的两个不同大脑区域--纹状体和海马体的蛋白酶体活性。结果表明，蛋白酶体的活性及其对蛋白酶体抑制剂的反应取决于蛋白酶体的亚细胞定位和脑区。用碘二醇梯度分离法分离蛋白酶体复合体，然后对蛋白酶体相互作用伙伴进行蛋白质组学分析。蛋白质组学结果揭示了大脑区域特异性的非蛋白酶体伙伴，包括伽马烯醇化酶(ENO2)。ENO2与从纹状体提纯的蛋白酶体复合体的联系比与从海马体提纯的蛋白酶体复合体的联系更密切。这些结果突出了蛋白酶体的非蛋白酶体伙伴在几个大脑区域记录的蛋白酶体复合体的不同活动方面的潜在关键作用。
Defects in the activity of the proteasome or its regulators are linked to several pathologies, including neurodegenerative diseases. We hypothesize that proteasome heterogeneity and its selective partners vary across brain regions and have a significant impact on proteasomal catalytic activities. Using neuronal cell cultures and brain tissues obtained from mice, we compared proteasomal activities from two distinct brain regions affected in neurodegenerative diseases, the striatum and the hippocampus. The results indicated that proteasome activities and their responses to proteasome inhibitors are determined by their subcellular localizations and their brain regions. Using an iodixanol gradient fractionation method, proteasome complexes were isolated, followed by proteomic analysis for proteasomal interaction partners. Proteomic results revealed brain region-specific non-proteasomal partners, including gamma-enolase (ENO2). ENO2 showed more association to proteasome complexes purified from the striatum than to those from the hippocampus. These results highlight a potential key role for non-proteasomal partners of proteasomes regarding the diverse activities of the proteasome complex recorded in several brain regions.
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