Enzymes or enzyme complexes can be concentrated in different cellular loci to modulate distinct functional processes in response to specific signals. How cells condense and compartmentalize enzyme complexes for spatiotemporally distinct cellular events is not well understood. Here we discover that specific and tight association of GIT1 and β-Pix, a pair of GTPase regulatory enzymes, leads to phase separation of the complex without additional scaffolding molecules. GIT1/β-Pix condensates are modular in nature and can be positioned at distinct cellular compartments, such as neuronal synapses, focal adhesions, and cell-cell junctions, by upstream adaptors. Guided by the structure of the GIT/PIX complex, we specifically probed the role of phase separation of the enzyme complex in cell migration and synapse formation. Our study suggests that formation of modular enzyme complex condensates via phase separation can dynamically concentrate limited quantities of enzymes to distinct cellular compartments for specific and optimal signaling.

可以将酶或酶复合物浓缩在不同的细胞基因座中，以响应于特定信号来调节不同的功能过程。对于时空上不同的细胞事件，细胞如何凝结和分隔酶复合物尚不清楚。在这里，我们发现GIT1和β-Pix（一对GTPase调节酶）之间的特异性紧密结合导致复合物的相分离，而没有其他支架分子。GIT1 /β-Pix缩合物本质上是模块化的，可以通过上游衔接子定位在不同的细胞区室，例如神经元突触，粘着斑和细胞间连接处。在GIT / PIX复合物的结构指导下，我们专门探讨了酶复合物的相分离在细胞迁移和突触形成中的作用。