Synapse Elimination Triggered by BMP4 Exocytosis and Presynaptic BMP Receptor Activation
Synapse Elimination Triggered by BMP4 Exocytosis and Presynaptic BMP Receptor Activation
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DOI：
10.1016/j.celrep.2017.12.101
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发表时间：
2018-01-23
期刊：
影响因子：
8.8
通讯作者：
Okabe, Shigeo
中科院分区：
文献类型：
--
作者：
Higashi, Takahito;Tanaka, Shinji;Okabe, Shigeo
在体外筛选参与神经回路形成的信号分子已经确定了大量的突触蛋白。然而，驱动突触消除的因素仍然难以捉摸。在这里，我们报告说，骨形态发生蛋白4（BMP 4）释放的轴突有能力消除突触。我们发现BMP4在致密核心囊泡中的快速轴突运输，其胞吐作用，以及随后通过突触附近的I型BMP受体的细胞表面聚集。培养中BMP 4过表达或敲除分别减少或增加突触前结构。表面BMP 4簇的不稳定作用仅限于附近的突触。在体内敲除BMP 4和随后的突触动力学的双光子成像证实了其在维持沿着轴突的突触前组分的适当密度中的关键作用。这些结果表明，在发育过程中，BMP 4在突触周围聚集在功能性神经元回路的构建中起着重要作用。
In vitro screening of signaling molecules involved in neural circuit formation has identified a large number of synaptogenic proteins. However, factors that drive synapse elimination remain elusive. Here, we report that bone morphogenetic protein 4 (BMP4) released from axons has the ability to eliminate synapses. We found fast axonal transport of BMP4 in dense-core vesicles, its exocytosis, and subsequent cell surface clustering via type I BMP receptors near synapses. BMP4 overexpression or knockout in culture reduced or increased presynaptic structures, respectively. The destabilizing effect of surface BMP4 clusters was limited to nearby synapses. In vivo knockout of BMP4 and subsequent two-photon imaging of synapse dynamics confirmed its critical role in maintaining an appropriate density of presynaptic components along the axon. These results suggest an essential role for perisynaptic clustering of BMP4 during development in the construction of functional neuronal circuits.