Jaruzelska Jadwiga, Kotecki Maciej, Kusz Kamila, Spik Anna, Firpo Meri, Reijo Pera Renee A
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, CA 94143-0546, USA.
Dev Genes Evol. 2003 Apr;213(3):120-6. doi: 10.1007/s00427-003-0303-2. Epub 2003 Feb 11.
Germ cells are the cells which ultimately give rise to mature sperm and eggs. In model organisms such as flies and worms, several genes that are required for formation and maintenance of germ cells have been identified and their interactions are rapidly being delineated. By contrast, little is known of the genes required for development of human germ cells and it is not clear whether findings from model organisms will translate into knowledge of human germ cell development, especially given observations that reproductive pathways may evolve more rapidly than somatic pathways. The Pumilio and Nanos genes have been especially well-characterized in model organisms and encode proteins that interact and are required for development of germ stem cells in one or both sexes. Here we report the first characterization of a mammalian Nanos homolog, human NANOS1 ( NOS1). We show that human NOS1 protein interacts with the human PUMILIO-2 (PUM2) protein via highly conserved domains to form a stable complex. We also show that in men, the NOS1 and PUM2 proteins are particularly abundant in germline stem cells. These observations mirror those in distant species and document for the first time a conserved protein-protein interaction in germ cells from flies to humans. These results suggest the possibility that the interaction of PUM2 and NOS1 may play a conserved role in germ cell development and maintenance in humans as in model organisms.
生殖细胞是最终产生成熟精子和卵子的细胞。在果蝇和线虫等模式生物中，已经鉴定出了几种生殖细胞形成和维持所需的基因，并且它们之间的相互作用也在迅速被阐明。相比之下，人们对人类生殖细胞发育所需的基因知之甚少，而且尚不清楚模式生物中的研究结果是否能转化为对人类生殖细胞发育的认识，特别是考虑到有观察表明生殖途径可能比体细胞途径进化得更快。Pumilio和Nanos基因在模式生物中得到了特别充分的表征，它们编码的蛋白质相互作用，并且是两性生殖干细胞发育所必需的。在此，我们报告了哺乳动物Nanos同源物——人类NANOS1（NOS1）的首次特征描述。我们发现人类NOS1蛋白通过高度保守的结构域与人类PUMILIO-2（PUM2）蛋白相互作用，形成一个稳定的复合物。我们还发现，在男性中，NOS1和PUM2蛋白在生殖系干细胞中特别丰富。这些观察结果与远缘物种中的情况相似，并首次证明了从果蝇到人类的生殖细胞中存在保守的蛋白质-蛋白质相互作用。这些结果表明，PUM2和NOS1之间的相互作用可能在人类生殖细胞发育和维持中发挥与模式生物中类似的保守作用。
