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.

蛋白酶体或其调节剂的活性缺陷与几种病理有关，包括神经退行性疾病。我们假设蛋白酶体异质性及其选择性伙伴因大脑区域而异，并对蛋白酶体催化活性产生重大影响。使用从小鼠获得的神经元细胞培养物和脑组织，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。结果表明蛋白酶体活性及其对蛋白酶体抑制剂的反应由它们的亚细胞定位和它们的大脑区域决定。使用碘克沙醇梯度分级分离法，分离蛋白酶体复合物，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 γ-烯醇化酶 (ENO2)。ENO2 与从纹状体中纯化的蛋白酶体复合物的关联性比与海马中的蛋白酶体复合物的关联性更高。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物的不同活动方面的潜在关键作用。