Department of Biochemistry and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Mol Cell Biol. 2010 May;30(9):2241-50. doi: 10.1128/MCB.01166-09. Epub 2010 Feb 22.
Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives the extending neurite, yet little is known of the molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation and morphogenesis, and BMP7 in particular induces the formation of dendrites. Here, we show that BMP7 induces stabilization of microtubules in both a MAP2-dependent neuronal cell culture model and in dendrites of primary cortical neurons. BMP7 rapidly activates c-Jun N-terminal kinases (JNKs), known regulators of microtubule dynamics, and we show that JNKs associate with the carboxy terminus of the BMP receptor, BMPRII. Activation and binding of JNKs to BMPRII is required for BMP7-induced microtubule stabilization and for BMP7-mediated dendrite formation in primary cortical neurons. These data indicate that BMPRII acts as a scaffold to localize and coordinate cytoskeletal remodeling and thereby provides an efficient means for extracellular cues, such as BMPs, to control neuronal dendritogenesis.
神经元的生长通过涉及肌动蛋白和微管的细胞骨架的协调重塑发生。微管的稳定驱动延伸的神经突，但对于细胞外信号调节微管动力学的分子机制知之甚少。骨形态发生蛋白 (BMPs) 在神经元分化和形态发生中发挥重要作用，特别是 BMP7 诱导树突的形成。在这里，我们表明 BMP7 在 MAP2 依赖性神经元细胞培养模型和原代皮质神经元的树突中诱导微管的稳定。BMP7 快速激活已知调节微管动力学的 c-Jun N 端激酶 (JNKs)，我们表明 JNKs 与 BMP 受体 BMPRII 的羧基末端结合。JNKs 的激活和与 BMPRII 的结合对于 BMP7 诱导的微管稳定以及 BMP7 介导的原代皮质神经元中的树突形成是必需的。这些数据表明 BMPRII 作为支架发挥作用，以定位和协调细胞骨架重塑，从而为细胞外信号（例如 BMPs）提供一种有效的方法来控制神经元树突发生。
