Anger M, Samuel J L, Marotte F, Wuytack F, Rappaport L, Lompré A M
INSERM U 275, LOA, ENSTA, Ecole Polytechnique, Palaiseau, France.
J Mol Cell Cardiol. 1994 Apr;26(4):539-50. doi: 10.1006/jmcc.1994.1064.
The Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) plays a crucial role in maintaining the Ca2+ homeostasis, which itself, controls various essential cellular function. The existence of several SERCA isoforms, encoded by three different genes and produced by alternative splicing of pre-mRNA transcripts, has been established by cDNA cloning. However, the temporo-spatial evolution of their expression during ontogeny was unknown. We have used in situ hybridization to determine the cellular distribution of three of these mRNA isoforms, SERCA 2a, SERCA 2b and SERCA 3 during rat ontogeny and focused our study on the cardiovascular system. We demonstrate that early in embryogenesis, SERCA 3 mRNA is highly expressed in the heart tube and is also present in the yolk sac. In 14-16 days embryos, SERCA 3 mRNA has disappeared from the heart but is expressed in the aorta and in discrete foci of the liver. Later on, its expression in the cardiovascular system is restricted to the arterial endothelium. SERCA 2a mRNA is coexpressed with SERCA 3 mRNA in the heart tube and remains expressed in the cardiomyocytes throughout life. It is transiently expressed in skeletal muscle at the onset of differentiation. In early foetal life, SERCA 2b is expressed in the mesenteric area and thereafter in all cell types at various levels. Our data indicate that (i) expression of SERCA 2b is neither tissue-specific nor developmentally regulated (ii) expression of SERCA 2a and SERCA 3 isoforms is regulated in a cell specific manner during development and suggest that the SERCA 3 gene plays a role in controlling the function of endothelial cells during vasculogenesis.
肌浆(内质)网Ca²⁺-ATP酶(SERCA)在维持Ca²⁺稳态中起关键作用,而Ca²⁺稳态本身控制着各种重要的细胞功能。通过cDNA克隆已证实存在由三个不同基因编码并由前体mRNA转录本的可变剪接产生的几种SERCA亚型。然而,它们在个体发育过程中表达的时空演变尚不清楚。我们利用原位杂交技术确定了大鼠个体发育过程中这三种mRNA亚型(SERCA 2a、SERCA 2b和SERCA 3)的细胞分布,并将研究重点放在心血管系统上。我们证明,在胚胎发育早期,SERCA 3 mRNA在心脏管中高度表达,并且也存在于卵黄囊中。在14 - 16天的胚胎中,SERCA 3 mRNA已从心脏消失,但在主动脉和肝脏的离散灶中表达。后来,其在心血管系统中的表达仅限于动脉内皮。SERCA 2a mRNA在心脏管中与SERCA 3 mRNA共表达,并在心肌细胞中终生表达。它在分化开始时在骨骼肌中短暂表达。在胎儿早期,SERCA 2b在肠系膜区域表达,此后在所有细胞类型中以不同水平表达。我们的数据表明:(i)SERCA 2b的表达既不是组织特异性的,也不受发育调控;(ii)SERCA 2a和SERCA 3亚型的表达在发育过程中以细胞特异性方式受到调控,并表明SERCA 3基因在血管生成过程中控制内皮细胞功能方面发挥作用。