Abstract:
A Disintegrin And Metalloprotease 10 (ADAM10), is able to control several important physiopathological processes through the shedding of a large number of protein substrates. Although ADAM10 plays a crucial role in the central nervous system (CNS) development and function, its protein distribution in the CNS has not been fully addressed. Here, we described the regional and cellular ADAM10 protein expression in C57BL/6 mice examined by immunofluorescence 1) throughout the adult mouse brain, cerebellum and spinal cord in vivo and 2) in different cell types as neurons, astrocytes, oligodendrocytes and microglia in vitro. We observed ADAM10 expression through the whole CNS, with a strong expression in the hippocampus, in the hypothalamus and in the cerebral and piriform cortex in the brain, in the Purkinje and in granular cell layers in the cerebellum and in the spinal cord to a lower extent. In vivo, ADAM10 protein expression was mainly found in neurons and in some oligodendroglial cell populations. However, in primary cultures we observed ADAM10 expression in neurons, oligodendrocytes, astrocytes and microglia. Interestingly, ADAM10 was not only found in the membrane but also in cytoplasmic vesicles and in the nucleus of primary cultured cells. Overall, this work highlights a wide distribution of ADAM10 throughout the CNS. The nuclear localization of ADAM10, probably due to its intracellular domain, emphasizes its role in cell signalling in physiological and pathological conditions. Further investigations are required to better elucidate the role of ADAM10 in glial cells.
摘要:
解整合素和金属蛋白酶10(ADAM10),能够通过大量蛋白质底物的脱落来控制几个重要的生理病理过程。尽管ADAM10在中枢神经系统(CNS)的发育和功能中起着至关重要的作用,其在中枢神经系统中的蛋白质分布尚未得到充分解决。这里,我们描述了通过免疫荧光1)在整个成年小鼠大脑中检查的C57BL/6小鼠中的区域和细胞ADAM10蛋白表达,体内小脑和脊髓,2)在不同的细胞类型中作为神经元,星形胶质细胞,体外少突胶质细胞和小胶质细胞。我们观察到ADAM10在整个中枢神经系统的表达,海马体有强烈的表情,在下丘脑,大脑和梨状皮层中,在浦肯野,小脑和脊髓的颗粒细胞层中较低。在体内,ADAM10蛋白表达主要在神经元和一些少突胶质细胞群中发现。然而,在原代培养物中,我们观察到ADAM10在神经元中的表达,少突胶质细胞,星形胶质细胞和小胶质细胞。有趣的是,ADAM10不仅存在于膜中,而且存在于胞质囊泡和原代培养细胞的细胞核中。总的来说,这项工作强调了ADAM10在整个中枢神经系统中的广泛分布。ADAM10的核定位,可能是由于其胞内结构域,强调其在生理和病理条件下的细胞信号传导中的作用。需要进一步的研究来更好地阐明ADAM10在神经胶质细胞中的作用。