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首页> 外文期刊>Journal of Cellular Physiology >Initiation of BMP2 signaling in domains on the plasma membrane
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Initiation of BMP2 signaling in domains on the plasma membrane

机译：BMP2的起始信号在域等离子体膜

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摘要

Bone morphogenetic protein 2 (BMP2) is a potent growth factor crucial for cell fate determination. It directs the differentiation of mesenchymal stem cells into osteoblasts, chondrocytes, adipocytes, and myocytes. Initiation of BMP2 signaling pathways occurs at the cell surface through type I and type II serine/threonine kinases housed in specific membrane domains such as caveolae enriched in the caveolin-1 beta isoform (CAV1β, caveolae) and clathrin-coated pits (CCPs). In order for BMP2 to initiate Smad signaling it must bind to its receptors on the plasma membrane resulting in the phosphorylation of the BMP type Ia receptor (BMPRIa) followed by activation of Smad signaling. The current model suggests that the canonical BMP signaling pathway, Smad, occurs in CCPs. However, several recent studies suggested Smad signaling may occur outside of CCPs. Here, we determined; (i) The location of BMP2 binding to receptors localized in caveolae, CCPs, or outside of these domains using AFM and confocal microscopy. (ii) The location of phosphorylation of BMPRIa on the plasma membrane using membrane fractionation, and (iii) the effect of down regulation of caveolae on Smad signaling. Our data indicate that BMP2 binds with highest force to BMP receptors (BMPRs) localized in caveolae. BMPRIa is phosphorylated in caveolae and the disruption of caveolae-inhibited Smad signaling in the presence of BMP2. This suggests caveolae are necessary for the initiation of Smad signaling. We propose an extension of the current model of BMP2 signaling, in which the initiation of Smad signaling is mediated by BMPRs in caveolae.
机译：骨形成蛋白2 (BMP2)是有效的生长因子细胞命运的关键的决心。间充质干细胞向成骨细胞,软骨细胞、脂肪细胞和细胞。BMP2信号通路发生在启动通过I型和II型细胞表面丝氨酸/苏氨酸激酶安置在具体膜域小窝丰富等caveolin-1β异构体(CAV1β,小窝)和clathrin-coated坑(ccp)。启动Smad信号必须绑定到它质膜上的受体磷酸化的BMP Ia型受体(BMPRIa)激活Smad紧随其后信号。规范BMP信号通路,Smad,发生在集中交易对手。Smad ccp以外的信号可能发生。我们决定;在小窝受体本地化,ccp,或在这些领域使用AFM和共焦显微镜。质膜上的BMPRIa使用膜分馏和(iii)的影响监管的小窝Smad信号。数据显示,BMP2结合最高的力量骨形态发生蛋白受体(BMPRs)本地化的小窝。BMPRIa小窝和磷酸化中断caveolae-inhibited Smad信号在BMP2的存在。发起Smad是必要的吗信号。BMP2模型信号,启动Smad信号是由BMPRs小窝。

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