肌浆网Ca2+-ATP酶在跨物种和胚层的细胞迁移和分支中发挥作用。
SERCA directs cell migration and branching across species and germ layers.
作者信息
Bower Danielle V, Lansdale Nick, Navarro Sonia, Truong Thai V, Bower Dan J, Featherstone Neil C, Connell Marilyn G, Al Alam Denise, Frey Mark R, Trinh Le A, Fernandez G Esteban, Warburton David, Fraser Scott E, Bennett Daimark, Jesudason Edwin C
机构信息
Division of Biological Sciences, California Institute of Technology, Pasadena, CA 91125, USA
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
出版信息
Biol Open. 2017 Oct 15;6(10):1458-1471. doi: 10.1242/bio.026039.
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in air sac budding. Live imaging of tracheogenesis revealed elevated Ca levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm ( nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca signaling, established by SERCA, in iterative budding.
分支形态发生是脊椎动物和无脊椎动物器官发生的基础，但目前尚未完全了解。在这里，我们表明肌浆网钙再摄取泵（SERCA）指导跨胚层和物种的出芽。克隆敲低证明了SERCA在气囊出芽中具有细胞自主作用。气管发生的实时成像显示，迁移的顶端细胞在形成分支时钙水平升高。SERCA阻断消除了这种钙差异，导致细胞迁移和新分支形成均停止。激活蛋白激酶C（PKC）可恢复顶端细胞中的钙水平，并恢复细胞迁移和分支。同样，抑制SERCA会消除哺乳动物上皮出芽，PKC激活可挽救出芽，而形态发生素则不能。中胚层（斑马鱼血管生成）和外胚层（神经系统）表现出相似的行为，这表明在迭代出芽过程中，由SERCA建立的细胞自主钙信号传导存在保守需求。
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