Combinatorial Signal Perception in the BMP Pathway.

Combinatorial Signal Perception in the BMP Pathway.
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DOI:
10.1016/j.cell.2017.08.015
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发表时间:
2017-09-07
期刊:
影响因子:
64.5
通讯作者:
Elowitz MB
Elowitz MB
中科院分区:
生物学1区
文献类型:
--
作者:
Antebi YE;Linton JM;Klumpe H;Bintu B;Gong M;Su C;McCardell R;Elowitz MB

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骨形态发生蛋白(BMP)信号传导途径包括多种配体和受体,这些配体和受体彼此相交,通常以组合形式出现。通常用冗余和调节灵活性来解释此功能,但仍不清楚它提供的信号处理功能。在这里,我们表明,BMP途径使用特定的计算曲目(包括比率传感,平衡检测和失衡检测)来处理多配体输入。这些计算在不同配体的相对水平上运行,并且可以直接来自竞争性受体配体相互作用。此外,细胞可以通过表达替代受体变体的表达来选择不同的计算以在相同的配体组合上执行。这些结果为混杂受体配体相互作用提供了直接的信号处理作用,并建立了用BMP配体定量控制细胞的操作原理。类似的原则可能适用于其他滥交信号通路。 通过利用BMP途径中的混杂受体配体相互作用,单个细胞可以根据受体配体的组合来执行不同的计算。
The Bone Morphogenetic Protein (BMP) signaling pathway comprises multiple ligands and receptors that interact promiscuously with one another, and typically appear in combinations. This feature is often explained in terms of redundancy and regulatory flexibility, but it has remained unclear what signal processing capabilities it provides. Here, we show that the BMP pathway processes multi-ligand inputs using a specific repertoire of computations, including ratiometric sensing, balance detection and imbalance detection. These computations operate on the relative levels of different ligands, and can arise directly from competitive receptor-ligand interactions. Furthermore, cells can select different computations to perform on the same ligand combination through expression of alternative sets of receptor variants. These results provide a direct signal processing role for promiscuous receptor-ligand interactions, and establish operational principles for quantitatively controlling cells with BMP ligands. Similar principles could apply to other promiscuous signaling pathways. By harnessing promiscuous receptor-ligand interactions in the BMP pathway a single cell can perform different computations depending on which combinations of receptor ligands are present.
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