Phase Separation in Cell Polarity

Abstract

Cells are biochemically and morphologically polarized, which allows them to produce different cell shapes for various functions. Remarkably, some polarity protein complexes are asymmetrically recruited and concentrated on limited membrane regions, which is essential for the establishment and maintenance of diverse cell polarity. Though the components and mutual interactions within these protein complexes have been extensively investigated, how these proteins autonomously concentrate at local membranes and whether they have the same organization mechanism in the condensed assembly as that in aqueous solution remain elusive. A number of recent studies suggest that these highly concentrated polarity protein assemblies are membraneless biomolecular condensates which form through liquid–liquid phase separation (LLPS) of specific proteins. In this perspective, we summarize the LLPS-driven condensed protein assemblies found in asymmetric cell division, epithelial cell polarity, and neuronal synapse formation and function. These findings suggest that LLPS may be a general strategy for cells to achieve local condensation of specific proteins, thus establishing cell polarity.

Phase Separation and Mechanical Forces in Regulating Asymmetric Cell Division of Neural Stem Cells

“…Recent studies have suggested that LLPS is a driving force of the autonomous assembly of the highly enriched protein crescents beneath the apical and basal cortex in dividing Drosophila NBs. Through domain recognition or oligomerization-mediated multivalent interactions, the Baz/Par3-Par-6-aPKC complex and the Numb-Pon complex (likely the Miranda-Pros-Staufen-Brat complex as well) form apical and basal protein condensates spatiotemporally, thus establishing the cell polarity and providing polarity cues for the following ACDrelated processes [74]. Compared with the classical membrane anchoring or clustering mechanism, the LLPS theory presents prominent advantages, the most important one being the high dynamics property of protein condensates, which is assumed to be essential for the fast response to cell-cycle signals to assemble or disassemble the cell polarity cues.…”

Contribution of the Testosterone Androgen Receptor–PARD3B Signaling Axis to Tumorigenesis and Malignance of Glioblastoma Multiforme through Stimulating Cell Proliferation and Colony Formation

“…Human glioblastoma cells were replated in 35 mm tissue culture dishes at a density of 10 3 cells per dish for 3 days. Colonies were stained with crystal violet, and then the colonies were counted and statistically analyzed as described previously [ 12 ].…”

“…Cell morphologies and shapes are produced through a polarity process [ 12 ]. Functionally, cell polarity can determine the division of asymmetric cells, vectorial transport of ions and molecules, and cell proliferation and migration [ 13 ].…”