Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains.
Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains.
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DOI：
10.1016/j.neuron.2015.11.011
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发表时间：
2015-12-16
期刊：
影响因子：
16.2
通讯作者：
Biederer T
中科院分区：
文献类型：
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作者：
Perez de Arce K;Schrod N;Metzbower SWR;Allgeyer E;Kong GK;Tang AH;Krupp AJ;Stein V;Liu X;Bewersdorf J;Blanpied TA;Lucić V;Biederer T
裂隙是突触不可或缺的一部分，但其大分子组织尚不清楚。我们在这里用冷冻电子断层扫描(Cryo-ET)测量到兴奋性突触的裂隙呈现出明显的密度分布。为了获得分子上的洞察力，我们分析了突触组织蛋白SynCAM1和EphB2。对SynCAM1基因敲除的突触和过表达的突触的冷冻-ET表明，这种免疫球蛋白形成了裂隙的边缘。一致地，SynCAM1描绘了免疫电子显微镜(EM)和超分辨率成像所确定的突触后周长。相反，EphB2受体酪氨酸激酶在突触后区域更深地富含。出乎意料的是，SynCAM 1可以在突触后密度附近形成集合，并且包含这些集合的突触更大。突触后突触后突触表面点状突触不是静止的，而是在长期抑郁后变大。这些结果支持突触裂隙在纳米尺度上被组织成由不同的跨突触复合体标记的亚室。
The cleft is an integral part of synapses, yet its macromolecular organization remains unclear. We here show that the cleft of excitatory synapses exhibits a distinct density profile as measured by cryo-electron tomography (cryo-ET). Aiming for molecular insights, we analyzed the synapse-organizing proteins SynCAM 1 and EphB2. Cryo-ET of SynCAM 1 knock-out and overexpressor synapses showed that this immunoglobulin protein shapes the cleft’s edge. In agreement, SynCAM 1 delineates the postsynaptic perimeter as determined by immuno-electron microscopy (EM) and superresolution imaging. In contrast, the EphB2 receptor tyrosine kinase is enriched deeper within the postsynaptic area. Unexpectedly, SynCAM 1 can form ensembles proximal to postsynaptic densities, and synapses containing these ensembles were larger. Postsynaptic SynCAM 1 surface puncta were not static but became enlarged after a long-term depression paradigm. These results support that the synaptic cleft is organized on a nanoscale into sub-compartments marked by distinct trans-synaptic complexes.