SMAD versus Non-SMAD Signaling Is Determined by Lateral Mobility of Bone Morphogenetic Protein (BMP) Receptors
SMAD versus Non-SMAD Signaling Is Determined by Lateral Mobility of Bone Morphogenetic Protein (BMP) Receptors
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DOI：
10.1074/jbc.m112.387639
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发表时间：
2012-11-16
影响因子：
4.8
通讯作者：
Knaus, Petra
中科院分区：
文献类型：
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作者：
Guzman, Asja;Zelman-Femiak, Monika;Knaus, Petra
骨（或身体）形态发生蛋白（BMP）属于TGF β超家族，对胚胎发育和器官形成以及成人组织稳态和修复至关重要。BMP受体通过其配体的活化导致诱导若干信号级联。使用荧光恢复后的光漂白，FRET，和单粒子跟踪显微镜，我们证明，BMP受体I型和II型（BMPRI和BMPRII）具有不同的横向流动性的质膜内，这是强制性的参与不同的信号通路。在配体结合之前，BMPRI和BMPRII的亚群表现出受限的运动，反映了预组装的异聚体受体复合物。第二自由扩散BMPRII群体仅在配体添加后变得受限。本文可视化时间分辨的BMP受体复合物的形成，并证明了BMPRI的横向流动性在稳定异聚体BMPRI-BMPRII受体复合物以差异刺激SMAD与非SMAD信号传导方面具有重大影响。
Bone (or body) morphogenetic proteins (BMPs) belong to the TGF beta superfamily and are crucial for embryonic patterning and organogenesis as well as for adult tissue homeostasis and repair. Activation of BMP receptors by their ligands leads to induction of several signaling cascades. Using fluorescence recovery after photobleaching, FRET, and single particle tracking microscopy, we demonstrate that BMP receptor type I and II (BMPRI and BMPRII) have distinct lateral mobility properties within the plasma membrane, which is mandatory for their involvement in different signaling pathways. Before ligand binding, BMPRI and a subpopulation of BMPRII exhibit confined motion, reflecting preassembled heteromeric receptor complexes. A second free diffusing BMPRII population only becomes restricted after ligand addition. This paper visualizes time-resolved BMP receptor complex formation and demonstrates that the lateral mobility of BMPRI has a major impact in stabilizing heteromeric BMPRI-BMPRII receptor complexes to differentially stimulate SMAD versus non-SMAD signaling.