Effect of the distribution and clustering of the type I A BMP receptor (ALK3) with the type II BMP receptor on the activation of signalling pathways
Effect of the distribution and clustering of the type I A BMP receptor (ALK3) with the type II BMP receptor on the activation of signalling pathways
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DOI：
10.1242/jcs.00519
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发表时间：
2003-08-15
影响因子：
4
通讯作者：
Petersen, NO
中科院分区：
文献类型：
--
作者：
Nohe, A;Keating, E;Petersen, NO
骨形态发生蛋白（BMPs）在胚胎发育过程中起重要作用，尤其是在软骨形成、骨形成、神经形成和造血过程中。在非洲人中已知有超过19种BMP，但迄今为止已知只有三种BMP-I型受体和三种BMP-II型受体介导这些反应。先前的报道提供了证据支持BMP受体的寡聚化影响下游BMP信号传导途径Smad或p38 MAPK途径的激活。为了进一步探索BMP受体聚集在信号传导中的重要性，图像相关光谱已被用于研究BMP受体在细胞膜表面的聚集和分布。在这里，我们证明了BMP-II型受体（BRII）的共表达影响了COS 7细胞和A431细胞中BMP-Ia型受体（BRIa）的聚集和分布。我们还表明，BMP-2刺激的细胞导致在细胞表面的受体复合物的重排。使用A431细胞和肢芽来源的间充质细胞，我们表明，BRII和组成性活性BRIa-ca的共表达是必要的Smad通路的激活。重要的是，使用激酶失活的BRII，BRIa的重排被阻断。总之，这些发现表明，在形成预先形成的配体独立复合物之前，细胞表面的受体重排在Smad通路的激活中起着关键作用。它还进一步表明，BRII的激酶活性是信号传导所需的，超出了BRIa在GS结构域的激活。
Bone morphogenetic proteins (BMPs) play an important role during embryonic development, especially in chondrogenesis, osteogenesis, neurogenesis and hematopoiesis. There are over 19 BMPs known in mammalians, but only three BMP-type-I receptors and three BMP-type-II receptors are known so far to mediate these responses. Previous reports provide evidence to support that oligomerisation of BMP receptors influences the activation of the downstream BMP signalling pathways, the Smad or the p38 MAPK pathway. To further explore the importance of BMP receptor clustering in signalling, image correlation spectroscopy has been used to investigate the clustering and distribution of BMP receptors at the surface of the cell membrane. Here we demonstrate that the co-expression of the BMP-type-II receptor (BRII) influences the aggregation and the distribution of the BMP-type-Ia receptor (BRIa) in COS7 cells and in A431 cells. We also demonstrate that BMP-2 stimulation of the cells leads to a rearrangement of receptor complexes at the cell surface. Using A431 cells and limb bud-derived mesenchymal cells, we show that co-expression of the BRII and a constitutive active BRIa-ca is necessary for the activation of the Smad pathway. Importantly using a kinase-inactive BRII the rearrangement of BRIa is blocked. Together, these findings suggest that rearrangement of the receptors at the cell surface prior to forming preformed ligand independent complexes plays a critical role in activation of the Smad pathway. It also suggests further that the kinase activity of BRII is needed for signalling beyond the activation of BRIa at the GS domain.