ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis.

ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis.
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DOI:
10.1371/journal.pone.0008198
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发表时间:
2009-12-08
期刊:
影响因子:
3.7
通讯作者:
Dodd J
Dodd J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Perron JC;Dodd J

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骨形态发生蛋白(Bone morphogenetic protein, BMP)诱发的细胞重新定向和趋化发生迅速,涉及细胞膜局部事件。这些快速过程背后的信号通路可能与BMP的经典转录反应不同,但BMP受体如何被利用来产生不同的细胞内机制尚不清楚。我们发现bmp7诱导的单核细胞趋化性依赖于典型II型BMP受体的活性。虽然三种典型的II型BMP受体在单核细胞中表达,但通过RNAi抑制受体亚基表达表明,ActRIIA和BMPRII(而不是ActRIIB)对于bmp7诱导的趋化性都是必需的,但对于BMP介导的诱导则不是单独需要的。此外,BMP7的趋化反应不涉及典型的smad4依赖性信号传导,而是通过pi3k依赖性信号传导起作用,说明通过受体的不同参与选择性激活不同的细胞内事件。我们提出了一种BMP受体复合物模型,其中ActRIIA和BMPRII受体亚基的协同活性选择性地介导对BMP7的趋化反应。
Bone morphogenetic protein (BMP)-evoked reorientation and chemotaxis of cells occurs with rapid onset and involves events local to the cell membrane. The signaling pathways underlying these rapid processes likely diverge from those mediating classical transcriptional responses to BMPs but it remains unclear how BMP receptors are utilized to generate distinct intracellular mechanisms. We show that BMP7-evoked chemotaxis of monocytic cells depends on the activity of canonical type II BMP receptors. Although the three canonical type II BMP receptors are expressed in monocytic cells, inhibition of receptor subunit expression by RNAi reveals that ActRIIA and BMPRII, but not ActRIIB, are each essential for BMP7-evoked chemotaxis but not required individually for BMP-mediated induction. Furthermore, the chemotactic response to BMP7 does not involve canonical Smad4-dependent signaling but acts through PI3K-dependent signaling, illustrating selective activation of distinct intracellular events through differential engagement of receptors. We suggest a model of a BMP receptor complex in which the coordinated activity of ActRIIA and BMPRII receptor subunits selectively mediates the chemotactic response to BMP7.
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