Krücken Jürgen, Epe Markus, Benten W Peter M, Falkenroth Nina, Wunderlich Frank
Division of Molecular Parasitology and Centre of Biological and Medical Research, Heinrich-Heine-University, Düsseldorf, Germany.
J Cell Biochem. 2005 Oct 1;96(2):339-48. doi: 10.1002/jcb.20552.
The IMAP/IAN family of AIG1-like GTPases is conserved among vertebrates and angiosperm plants and has been postulated to regulate apoptosis, particularly in context with diseases such as cancer, diabetes, and infections. The human genes were recently renamed as gimap for GTPase of the immunity associated protein (GIMAP) family. Here we extend this new nomenclature to the murine gimap gene family. All gimap genes of the mouse are clustered on chromosome 6B with eight functional members and one pseudogene. The mGIMAP proteins contain one GTP-binding site and display molecular masses between 33 and 38 kDa except for the very unusual 77 kDa mGIMAP8 protein, which is the first characterized protein containing three GTP-binding domains. Northern blot analysis revealed expression of mgimap8 predominantly in the thymus. The low expression level observed in the spleen was further suppressed by Plasmodium chabaudi malaria. Confocal laser scanning microscopy demonstrated localization of mGIMAP8 at ER, Golgi, and mitochondria. Overexpression of mGIMAP8 could significantly impair anisomycin-induced activation of caspase 3. Our data support the view that mGIMAP8 exerts an anti-apoptotic effect in the immune system and is involved in responses to infections.
AIG1样GTP酶的IMAP/IAN家族在脊椎动物和被子植物中保守，据推测可调节细胞凋亡，特别是在癌症、糖尿病和感染等疾病的背景下。人类基因最近被重新命名为免疫相关蛋白（GIMAP）家族的GTP酶，即gimap。在这里，我们将这个新命名法扩展到小鼠gimap基因家族。小鼠的所有gimap基因都聚集在6B染色体上，有八个功能成员和一个假基因。mGIMAP蛋白含有一个GTP结合位点，分子量在33至38 kDa之间，除了非常特殊的77 kDa的mGIMAP8蛋白，它是第一个被鉴定出含有三个GTP结合结构域的蛋白。Northern印迹分析显示mgimap8主要在胸腺中表达。在脾脏中观察到的低表达水平在感染沙氏疟原虫疟疾后进一步受到抑制。共聚焦激光扫描显微镜显示mGIMAP8定位于内质网、高尔基体和线粒体。mGIMAP8的过表达可显著削弱茴香霉素诱导的caspase 3激活。我们的数据支持这样的观点，即mGIMAP8在免疫系统中发挥抗凋亡作用，并参与对感染的反应。
