Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, F-31062, Toulouse, France.
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The HKUST, Clear Water Bay, Hong Kong, PRC.
Sci Rep. 2019 Nov 5;9(1):16049. doi: 10.1038/s41598-019-52556-0.
In amphibians, the inhibition of bone morphogenetic protein (BMP) in the dorsal ectoderm has been proposed to be responsible for the first step of neural specification, called neural induction. We previously demonstrated that in Xenopus laevis embryos, the BMP signalling antagonist, noggin, triggers an influx of Ca through voltage-dependent L-type Ca channels (LTCCs), mainly via Ca1.2, and we showed that this influx constitutes a necessary and sufficient signal for triggering the expression of neural genes. However, the mechanism linking the inhibition of BMP signalling with the activation of LTCCs remained unknown. Here, we demonstrate that the transient receptor potential canonical subfamily member 1, (Trpc1), is an intermediate between BMP receptor type II (BMPRII) and the Ca1.2 channel. We show that noggin induces a physical interaction between BMPRII and Trpc1 channels. This interaction leads to the activation of Trpc1 channels and to an influx of cations, which depolarizes the plasma membrane up to a threshold sufficient to activate Cav1.2. Together, our results demonstrate for the first time that during neural induction, Ca entry through the Ca1.2 channel results from the noggin-induced interaction between Trpc1 and BMPRII.
在两栖动物中，背侧外胚层中骨形态发生蛋白（BMP）的抑制被认为是神经特化的第一步，即神经诱导。我们之前证明，在非洲爪蟾胚胎中，BMP 信号拮抗剂 noggin 通过电压依赖性 L 型钙通道（LTCCs）引发钙内流，主要通过 Ca1.2，并且我们表明这种内流构成了触发神经基因表达的必要和充分信号。然而，将 BMP 信号抑制与 LTCCs 的激活联系起来的机制仍然未知。在这里，我们证明瞬时受体电位经典亚家族成员 1（Trpc1）是 BMP 受体 II 型（BMPRII）和 Ca1.2 通道之间的中间物。我们表明 noggin 诱导 BMPRII 和 Trpc1 通道之间的物理相互作用。这种相互作用导致 Trpc1 通道的激活和阳离子内流，使质膜去极化至足以激活 Cav1.2 的阈值。总之，我们的结果首次证明，在神经诱导过程中，通过 Ca1.2 通道的钙内流是 noggin 诱导的 Trpc1 和 BMPRII 之间相互作用的结果。
