Cohen Tsadok, Ravid Liat, Altman Netta, Madar-Shapiro Liora, Fein Amos, Weil Miguel, Horowitz Mia
Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):8-19. doi: 10.1016/j.molbrainres.2004.06.027.
Prosaposin is the precursor of four lysosomal activator molecules known as saposins A, B, C and D. It is also secreted and was proposed to be a neurotrophic factor. The neurotrophic function was attributed to the amino terminus of saposin C. In man, mouse and rat prosaposin is transcribed to two major isoforms differing in the inclusion of 9 bps of exon 8 within the saposin B domain. In the present study, we show that there is evolutionary conservation of the prosaposin structure and alternative splicing in chick and zebrafish as well. Moreover, there is conservation in prosaposin expression as tested immunohistochemically in the mouse and chick developing brain. We developed a sensitive assay to quantitate the prosaposin alternatively spliced forms. Our results indicate that, in mouse brain, skeletal and cardiac muscle the exon 8-containing RNA is most abundant, while it is almost absent from visceral and smooth muscle-containing organs. We observed temporal and differential expression of the alternatively spliced prosaposin mRNAs in mouse and chick brain as well as during development. The elevation in the abundance of exon 8-containing prosaposin RNA during mouse and chick brain development may suggest a role for the exon 8-containing prosaposin form in this process.
鞘脂激活蛋白原是四种溶酶体激活分子（即鞘脂激活蛋白A、B、C和D）的前体。它也会被分泌出来，并被认为是一种神经营养因子。神经营养功能归因于鞘脂激活蛋白C的氨基末端。在人类、小鼠和大鼠中，鞘脂激活蛋白原转录产生两种主要的异构体，它们在鞘脂激活蛋白B结构域中是否包含外显子8的9个碱基对方面存在差异。在本研究中，我们表明，在鸡和斑马鱼中，鞘脂激活蛋白原的结构和可变剪接也存在进化保守性。此外，在小鼠和鸡发育中的大脑中进行免疫组织化学检测时，鞘脂激活蛋白原的表达也具有保守性。我们开发了一种灵敏的检测方法来定量鞘脂激活蛋白原的可变剪接形式。我们的结果表明，在小鼠脑、骨骼肌和心肌中，含外显子8的RNA最为丰富，而在内脏和含平滑肌的器官中几乎不存在。我们观察到小鼠和鸡大脑中以及发育过程中可变剪接的鞘脂激活蛋白原mRNA的时间和差异表达。在小鼠和鸡大脑发育过程中，含外显子8的鞘脂激活蛋白原RNA丰度的升高可能表明含外显子8的鞘脂激活蛋白原形式在这一过程中发挥作用。
