State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Mol Cell. 2020 Sep 3;79(5):782-796.e6. doi: 10.1016/j.molcel.2020.07.004. Epub 2020 Aug 10.
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.
酶或酶复合物可以集中在不同的细胞位置，以响应特定信号来调节不同的功能过程。细胞如何浓缩和区室化酶复合物，以实现时空上不同的细胞事件，目前还不是很清楚。在这里，我们发现 GIT1 和 β-Pix（一对 GTPase 调节酶）的特异性和紧密结合导致了复合物的相分离，而不需要额外的支架分子。GIT1/β-Pix 凝聚物具有模块性质，可以通过上游衔接蛋白定位到不同的细胞区室，如神经元突触、焦点黏附物和细胞-细胞连接处。受 GIT/PIX 复合物结构的指导，我们专门研究了酶复合物相分离在细胞迁移和突触形成中的作用。我们的研究表明，通过相分离形成模块化的酶复合物凝聚物可以动态地将有限数量的酶浓缩到不同的细胞区室，以实现特定和最佳的信号传递。
