Manetto V, Abdul-Karim F W, Perry G, Tabaton M, Autilio-Gambetti L, Gambetti P
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Am J Pathol. 1989 Mar;134(3):505-13.
The authors have shown previously that ubiquitin, a protein involved in the degradation of short-lived and abnormal proteins, is present in several cytoplasmic inclusions of neurons. This study used a library of antibodies to ubiquitin and immunohistochemically examined for the presence of ubiquitin in nonviral intracytoplasmic inclusions that form in different cell types under various pathologic conditions. Membrane-bound lysosomal and nonlysosomal inclusions such as those of storage disease, Russell bodies, alpha-1-antitrypsin and alpha-fetoprotein as well as nonmembrane-bound inclusions were examined. Ubiquitin epitopes were detected in some of the nonmembrane-bound inclusions only. The ubiquitin-containing inclusions were the Rosenthal fibers, Mallory bodies, Crooke bodies, Lafora bodies, amyloid bodies, and the giant axons of giant axonal neuropathy. Nemaline bodies and the inclusions of juvenile digital fibromatosis, both of which contain actin and actinbinding proteins, did not show immunoreaction. These findings, as well as those of the previous study, show that the presence of ubiquitin in cellular inclusions is selective. The ubiquitin-containing inclusions are not membrane bound; they are fibrillary and most contain also intermediate filament-related proteins. The role of ubiquitin in the formation of these inclusions remains to be elucidated.
作者们之前已经表明，泛素这种参与短命和异常蛋白质降解的蛋白质，存在于神经元的几种胞质内含物中。本研究使用了一个泛素抗体文库，并通过免疫组织化学方法检测在各种病理条件下不同细胞类型中形成的非病毒性胞质内含物中泛素的存在情况。对膜结合的溶酶体和非溶酶体内含物（如贮积病、拉塞尔小体、α-1抗胰蛋白酶和甲胎蛋白的内含物）以及非膜结合内含物进行了检测。仅在一些非膜结合内含物中检测到泛素表位。含泛素的内含物有罗森塔尔纤维、马洛里小体、克鲁克小体、拉福拉小体、淀粉样小体以及巨大轴索神经病的巨大轴突。肌动蛋白小体以及青少年指纤维瘤病的内含物，这两者都含有肌动蛋白和肌动蛋白结合蛋白，未显示免疫反应。这些发现以及之前研究的结果表明，细胞内含物中泛素的存在是具有选择性的。含泛素的内含物是非膜结合的；它们呈纤维状，并且大多数还含有中间丝相关蛋白。泛素在这些内含物形成中的作用仍有待阐明。
