Bundschu Karin, Schuh Kai
Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany.
Dev Dyn. 2014 May;243(5):699-711. doi: 10.1002/dvdy.24102. Epub 2014 Jan 22.
ATIPs (Angiotensin receptor type 2 [AT2] interacting proteins) are described as AT2 interacting protein variants, whereas their expression and functions during development are not known yet.
Here, we provide a detailed expression pattern of ATIP variants during mouse development by visualizing Mtus1 promotor activity, Mtus1 RNA, and subsequent ATIP protein expression. ATIPs are strongly expressed in the developing cardiovascular system, including the vascular plexus of the yolk sac and the fetal vascular part of the placenta. Moreover, ATIP is expressed spatially distinct during eye and limb bud development, and in later stages in lung and nervous system. The three murine ATIP isoforms are expressed in a distinct manner, whereupon isoform 1 and 4 are correlated to cardiovascular, lung, and limb bud development and isoform 3 is restricted to brain and eye development. Interestingly, Mtus1 expression is not necessarily correlated to Agtr2 expression, suggesting novel but yet unknown functions for ATIP, independent of AT2 signaling.
ATIPs seem to be mainly involved in the developmental regulation of the cardiovascular system and may act in different AT2-dependent and -independent manners. Hence, these results deliver valuable information to further elucidate the different functions of ATIPs in the processes of mammalian development.
血管紧张素2型受体（AT2）相互作用蛋白（ATIPs）被描述为AT2相互作用蛋白变体，然而其在发育过程中的表达和功能尚不清楚。
在此，我们通过可视化Mtus1启动子活性、Mtus1 RNA以及随后的ATIP蛋白表达，详细展示了小鼠发育过程中ATIP变体的表达模式。ATIPs在发育中的心血管系统中强烈表达，包括卵黄囊的血管丛和胎盘的胎儿血管部分。此外，ATIP在眼睛和肢芽发育过程中以及在后期的肺和神经系统中呈空间特异性表达。三种小鼠ATIP异构体以不同方式表达，其中异构体1和4与心血管、肺和肢芽发育相关，而异构体3则局限于脑和眼发育。有趣的是，Mtus1表达不一定与Agtr2表达相关，这表明ATIP具有独立于AT2信号传导的新的未知功能。
ATIPs似乎主要参与心血管系统的发育调控，可能以不同的依赖和不依赖AT2的方式发挥作用。因此，这些结果为进一步阐明ATIPs在哺乳动物发育过程中的不同功能提供了有价值的信息。
