AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells
AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells
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DOI：
10.1091/mbc.e19-03-0179
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发表时间：
2020-01-15
影响因子：
3.3
通讯作者：
Knaus, Petra
中科院分区：
文献类型：
--
作者：
Brunner, Patrizia;Hastar, Nurcan;Knaus, Petra
跨膜蛋白血管动蛋白（AMOT 130）的大同种型控制许多细胞类型的细胞增殖和迁移。AMOT 130与肌动蛋白细胞骨架相关，并通常通过紧密连接处极性蛋白的内体摄取来调节紧密连接的维持和信号传导。AMOT 130是高度极化的，并且仅存在于极化细胞的顶侧。在这里，我们表明骨形态发生蛋白（BMP）生长因子信号传导和AMOT功能在顶部-基底部极化细胞中相互关联。BMP 6控制上皮细胞中的AMOT内化和内体运输。AMOT 130与BMP受体BMPR 2相互作用，促进SMAD激活和靶基因表达。我们进一步证明了AMOT对BMP-SMAD信号传导的这种作用依赖于内吞作用，并且特异于极化上皮细胞和内皮细胞的顶侧。AMOT的敲低仅从极化细胞的顶侧减少SMAD信号传导，而基底侧BMP-SMAD信号传导不受影响。这允许第一次以极化方式干扰BMP信号传导，并将AMOT 130鉴定为新型BMP信号传导调节剂。
The large isoform of the transmembrane protein angiomotin (AMOT130) controls cell proliferation and migration of many cell types. AMOT130 associates to the actin cytoskeleton and regulates tight-junction maintenance and signaling often via endosomal uptake of polarity proteins at tight junctions. AMOT130 is highly polarized and present only at the apical side of polarized cells. Here we show that bone morphogenetic protein (BMP) growth factor signaling and AMOT function are interlinked in apical-basal polarized cells. BMP6 controls AMOT internalization and endosomal trafficking in epithelial cells. AMOT130 interacts with the BMP receptor BMPR2 and facilitates SMAD activation and target gene expression. We further demonstrate that this effect of AMOT on BMP-SMAD signaling is dependent on endocytosis and specific to the apical side of polarized epithelial and endothelial cells. Knockdown of AMOT reduces SMAD signaling only from the apical side of polarized cells, while basolateral BMP-SMAD signaling is unaffected. This allows for the first time interference with BMP signaling in a polarized manner and identifies AMOT130 as a novel BMP signaling regulator.