Institute for Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany.
J Biol Chem. 2012 Nov 16;287(47):39492-504. doi: 10.1074/jbc.M112.387639. Epub 2012 Sep 7.
Bone (or body) morphogenetic proteins (BMPs) belong to the TGFβ 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.
骨形态发生蛋白（BMPs）属于 TGFβ 超家族，对于胚胎形态发生和器官发生以及成人组织稳态和修复至关重要。其配体激活 BMP 受体后，会诱导多种信号级联反应。通过荧光恢复后漂白、FRET 和单颗粒跟踪显微镜，我们证明 BMP 受体 I 型和 II 型（BMPRI 和 BMPRII）在质膜内具有不同的横向流动性，这是它们参与不同信号通路的必要条件。在配体结合之前，BMPRI 和 BMPRII 的亚群表现出受限的运动，反映了预先组装的异源二聚体受体复合物。只有在添加配体后，第二个自由扩散的 BMPRII 群体才会受到限制。本文可视化了 BMP 受体复合物的形成过程，并表明 BMPRI 的横向流动性对于稳定异源二聚体 BMPRI-BMPRII 受体复合物以差异刺激 SMAD 与非 SMAD 信号转导具有重大影响。
