Isoform-specific cleavage of neuroligin-3 reduces synapse strength
Isoform-specific cleavage of neuroligin-3 reduces synapse strength
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DOI：
10.1038/s41380-018-0242-y
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发表时间：
2019-01-01
影响因子：
11
通讯作者：
Roche, Katherine W.
中科院分区：
文献类型：
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作者：
Bemben, Michael A.;Nguyen, Thien A.;Roche, Katherine W.
突触的组装和维持是动态的过程，需要突触前和突触后结构之间的双向接触。黏附分子网络调节神经元之间的这种物理相互作用。突触是如何分解的，以及是否存在控制特定黏附分子移除的不同机制，目前尚不清楚。在这里，我们报告了神经连接蛋白-3在突触活性和蛋白激酶C信号导致突触强度降低的反应中的异构体特异性蛋白分解。虽然神经连接蛋白-1和神经连接蛋白-2不直接被这一途径切割，但当它们与神经连接蛋白-3异源二聚时，它们也会发生蛋白水解性切割。因此，蛋白激酶C依赖的切割是通过神经连接蛋白-3介导的。最近对神经胶质瘤的研究表明，神经连接蛋白-3胞外结构域是一种有丝分裂原。在这里，我们证明：(1)存在控制特定黏附分子重塑的机制；(2)神经连接蛋白-3是神经连接蛋白切割事件的关键调节因子；以及(3)有两种切割途径：基础的和活性依赖的，它们产生神经连接蛋白-3的有丝分裂形式。
The assembly and maintenance of synapses are dynamic processes that require bidirectional contacts between the pre- and postsynaptic structures. A network of adhesion molecules mediate this physical interaction between neurons. How synapses are disassembled and if there are distinct mechanisms that govern the removal of specific adhesion molecules remain unclear. Here, we report isoform-specific proteolytic cleavage of neuroligin-3 in response to synaptic activity and protein kinase C signaling resulting in reduced synapse strength. Although neuroligin-1 and neuroligin-2 are not directly cleaved by this pathway, when heterodimerized with neuroligin-3, they too undergo proteolytic cleavage. Thus protein kinase C-dependent cleavage is mediated through neuroligin-3. Recent studies on glioma implicate the neuroligin-3 ectodomain as a mitogen. Here we demonstrate: (1) there are mechanisms governing specific adhesion molecule remodeling; (2) neuroligin-3 is a key regulator of neuroligin cleavage events; and (3) there are two cleavage pathways; basal and activity-dependent that produce the mitogenic form of neuroligin-3.