Cupit Pauline M, Hansen John D, McCarty Aaron S, White Greg, Chioda Mariacristina, Spada Fabio, Smale Stephen T, Cunningham Charles
Sars International Centre for Marine Molecular Biology, High Technology Centre, Bergen, Norway.
J Immunol. 2003 Dec 1;171(11):6006-13. doi: 10.4049/jimmunol.171.11.6006.
The Ikaros multigene family encodes a number of zinc finger transcription factors that play key roles in vertebrate hemopoietic stem cell differentiation and the generation of B, T, and NK cell lineages. In this study, we describe the identification and characterization of an Ikaros family-like (IFL) protein from the agnathan hagfish Myxine glutinosa and the marine urochordate Oikopleura dioica, both of which lie on the evolutionary boundary between the vertebrates and invertebrates. The IFL molecules identified in these animals displayed high conservation in the zinc finger motifs critical for DNA binding and dimerization in comparison with those of jawed vertebrates. Expression of the IFL gene in hagfish was strongest in blood, intestine, and gills. In O. dioica, transcription from the IFL gene was initiated at or around the time of hatching and maintained throughout the life span of the animal. In situ hybridization localized O. dioica IFL expression to the Fol cells, which are responsible for generating the food filter of the house. Biochemical analysis of the DNA binding and dimerization domains from M. glutinosa and O. dioici IFLs showed that M. glutinosa behaves as a true Ikaros family member. Taken together, these results indicate that the properties associated with the Ikaros family preceded the emergence of the jawed vertebrates and thus adaptive immunity.
伊卡洛斯多基因家族编码多种锌指转录因子,这些因子在脊椎动物造血干细胞分化以及B细胞、T细胞和自然杀伤细胞谱系的产生过程中发挥关键作用。在本研究中,我们描述了从无颌类盲鳗黏液黏盲鳗和海洋尾索动物住囊虫中鉴定和表征的一种伊卡洛斯家族样(IFL)蛋白,这两种动物都处于脊椎动物和无脊椎动物的进化边界上。与有颌脊椎动物相比,在这些动物中鉴定出的IFL分子在对DNA结合和二聚化至关重要的锌指基序中表现出高度保守性。IFL基因在盲鳗的血液、肠道和鳃中表达最强。在住囊虫中,IFL基因的转录在孵化时或孵化前后开始,并在动物的整个生命周期中持续存在。原位杂交将住囊虫IFL的表达定位到Fol细胞,这些细胞负责生成住室的食物过滤器。对黏液黏盲鳗和住囊虫IFL的DNA结合和二聚化结构域的生化分析表明,黏液黏盲鳗表现为真正的伊卡洛斯家族成员。综上所述,这些结果表明,与伊卡洛斯家族相关的特性在有颌脊椎动物出现之前就已存在,因此也早于适应性免疫。