Wiegand Tina, Liu Jinghui, Vogeley Lutz, LuValle-Burke Isabel, Geisler Jan, Fritsch Anatol W, Hyman Anthony A, Grill Stephan W
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
Max Planck Institute for the Physics of Complex Systems, Dresden 01187, Germany.
Proc Natl Acad Sci U S A. 2024 Dec 10;121(50):e2407497121. doi: 10.1073/pnas.2407497121. Epub 2024 Dec 4.
Cortical condensates, transient punctate-like structures rich in actin and the actin nucleation pathway member Neural Wiskott-Aldrich syndrome protein (N-WASP), form during activation of the actin cortex in the oocyte. Their emergence and spontaneous dissolution is linked to a phase separation process driven by chemical kinetics. However, the mechanisms that drive the onset of cortical condensate formation near membranes remain unexplored. Here, using a reconstituted phase separation assay of cortical condensate proteins, we demonstrate that the key component, N-WASP, can collectively undergo surface condensation on supported lipid bilayers via a prewetting transition. Actin partitions into the condensates, where it polymerizes and counteracts the N-WASP prewetting transition. Taken together, the dynamics of condensate-assisted cortex formation appear to be controlled by a balance between surface-assisted condensate formation and polymer-driven condensate dissolution. This opens perspectives for understanding how the formation of complex intracellular structures is affected and controlled by phase separation.
皮质凝聚物是一种富含肌动蛋白和肌动蛋白成核途径成员神经维斯科特-奥尔德里奇综合征蛋白(N-WASP)的瞬时点状结构,在卵母细胞的肌动蛋白皮质激活过程中形成。它们的出现和自发溶解与化学动力学驱动的相分离过程有关。然而,驱动膜附近皮质凝聚物形成起始的机制仍未得到探索。在这里,我们使用皮质凝聚物蛋白的重构相分离测定法,证明关键成分N-WASP可以通过预湿转变在支撑脂质双分子层上集体发生表面凝聚。肌动蛋白分配到凝聚物中,在那里它聚合并抵消N-WASP预湿转变。综上所述,凝聚物辅助皮质形成的动力学似乎由表面辅助凝聚物形成和聚合物驱动的凝聚物溶解之间的平衡控制。这为理解复杂细胞内结构的形成如何受到相分离的影响和控制开辟了新的视角。