Abstract：
Excitatory and inhibitory synapses do not overlap even when formed on one submicron-sized dendritic protrusion. How excitatory and inhibitory postsynaptic cytomatrices or densities (e/iPSDs) are segregated is not understood. Broadly, why membraneless organelles are naturally segregated in cellular subcompartments is unclear. Using biochemical reconstitutions in vitro and in cells, we demonstrate that ePSDs and iPSDs spontaneously segregate into distinct condensed molecular assemblies through phase separation. Tagging iPSD scaffold gephyrin with a PSD-95 intrabody (dissociation constant ~4 nM) leads to mistargeting of gephyrin to ePSD condensates. Unexpectedly, formation of iPSD condensates forces the intrabody-tagged gephyrin out of ePSD condensates. Thus, instead of diffusion-governed spontaneous mixing, demixing is a default process for biomolecules in condensates. Phase separation can generate biomolecular compartmentalization specificities that cannot occur in dilute solutions.
摘要：
即使在一个亚微米大小的树突状突起上形成，兴奋性和抑制性突触也不会重叠。尚不了解兴奋性和抑制性突触后细胞基质或密度（e/iPSD）如何分离。广义上,为什么无膜细胞器在细胞亚区室中自然隔离尚不清楚。使用体外和细胞中的生化重建，我们证明了ePSD和iPSD通过相分离自发地分离成不同的凝聚分子组装体。用PSD-95内抗体标记iPSD支架gephyrin（解离常数〜4nM）导致gephyrin对ePSD缩合物的误定。出乎意料的是,iPSD凝析油的形成迫使带抗体内标记的gephyrin脱离ePSD凝析油。因此，而不是扩散控制的自发混合，去混合是冷凝物中生物分子的默认过程。相分离可以产生在稀溶液中不能发生的生物分子区室化特异性。
