Apical-basal Polarity Research Articles

Three-dimensional spheroid culture induces apical-basal polarity and the original characteristics of immortalized human renal proximal tubule epithelial cells

The proximal tubules, which are part of the kidney, maintain blood homeostasis by absorbing amino acids, glucose, water, and ions such as sodium (Na), potassium, and bicarbonate. Proximal tubule dysfunction is associated with the pathogenesis of many kidney diseases. Renal proximal tubular epithelial cells (RPTECs) are responsible for the main functions of the proximal tubules. Therefore, in vitro experiments using RPTECs would greatly enhance our understanding of nephron physiology and pathobiology. It is preferable to use immortalized cell lines, such as human kidney-2 (HK-2) cells, because they are derived from humans and maintain growth indefinitely. However, tissue-specific RPTEC phenotypes, including apical-basal polarization, are frequently lost in conventional two-dimensional culture methods in part due to microenvironmental deficiencies. To overcome this limitation, we developed a three-dimensional (3D) spheroid culture method for HK-2 cells using an extracellular matrix. HK-2 spheroids in 3D culture formed a tubule-like architecture with cellular polarity and showed markedly restored Na transport function. 3D culture of HK-2 cells also increased expression of kidney development–related genes, including WNT9B. Models of human renal tubules using HK-2 spheroids will greatly improve our understanding of the physiology and pathobiology of the kidney.

E-Cadherin/HMR-1 Membrane Enrichment Is Polarized by WAVE-Dependent Branched Actin.

Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.

Scrib module proteins: Control of epithelial architecture and planar spindle orientation.

The Scrib module proteins, Scrib, Dlg, and Lgl, are conserved regulators of cell polarity in diverse biological contexts. Originally discovered as neoplastic tumor suppressors in the fruit fly Drosophila melanogaster, disruption of Scrib module components leads to tumorigenesis in mammalian epithelia and is associated with human cancers. With multiple protein interacting domains, Scrib module proteins function as determinants of basolateral identity in epithelial cells with apical-basal polarity while acting as signaling platform scaffold proteins. Recent studies have further revealed novel roles of the Scrib module in the control of epithelial architecture, ranging from polarity establishment and tricellular junction formation to planar spindle orientation during cell division. This review updates the current understanding of the molecular nature and physiological functions of the Scrib module with a focus on in vivo studies, providing a framework for how these protein dynamics affect the processes of epithelial organization.

A liquid culture cancer spheroid model reveals low PI3K/Akt pathway activity and low adhesiveness to the extracellular matrix.

Three-dimensional (3D) cultures of cancer cells in liquid without extracellular matrix (ECM) offer invitro models for metastasising conditions such as those in vessels and effusion. However, liquid culturing is often hindered by cell adhesiveness, which causes large cell clumps. We previously described a liquid culture material, LA717, which prevents nonclonal cell adhesion and subsequent clumping, thus allowing clonal growth of spheroids in an anchorage-independent manner. Here, we examined such liquid culture cancer spheroids for the acquisition of apical-basal polarity, sensitivity to an Akt inhibitor (anticancer drug MK-2206) and interaction with ECM. The spheroids present apical plasma membrane on the surface, which originated from the failure of polarisation at the single-cell stage and subsequent defects in phosphorylated ezrin accumulation at the cell boundary during the first cleavage, failing internal lumen formation. At the multicellular stage, liquid culture spheroids presented bleb-like protrusion on the surface, which was enhanced by the activation of the PI3K/Akt pathway and reduced by PI3K/Akt inhibitors. Liquid culture spheroids exhibited slow proliferation speed and low endogenous pAkt levels compared with gel-cultured spheroids and 2D-cultured cells, explaining the susceptibility to the Akt-inhibiting anticancer drug. Subcutaneous xenografting and invitro analysis demonstrated low viability and adhesive property of liquid culture spheroids to ECM, while migratory and invasive capacities were comparable with gel-cultured spheroids. These features agree with the low efficacy of circulating tumour spheroids in the settling step of metastasis. This study demonstrates the feature of anchorage-independent spheroids and validates liquid cultures as a useful method in cancer spheroid research.

E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers

Epithelial–mesenchymal transition (EMT) is an essential biological process involved in the initiation and progression of cancer by which epithelial tumor cells lose their differentiated characteristics, such as cell–cell adhesion and apical–basal polarity and acquire a more invasive and/or metastatic mesenchymal phenotype. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. In the case of SCC, the statistical analysis indicated significant differences of E-cadherin and Slug with the degree of tumor differentiation, and for fibronectin and Slug with the depth of invasion. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug, and in SCC a significant negative linear relation between E-cadherin/fibronectin, E-cadherin/Slug and a positive linear one in the case of fibronectin/Slug. The study indicates through the statistically significant relation between E-cadherin/fibronectin and E-cadherin/Slug, the EMT intervention in carcinogenesis of NMSC.

Apical-basal polarity regulators are essential for slit diaphragm assembly and endocytosis in Drosophila nephrocytes

Apical-basal polarity is a key feature of most epithelial cells and it is regulated by highly conserved protein complexes. In mammalian podocytes, which emerge from columnar epithelial cells, this polarity is preserved and the tight junctions are converted to the slit diaphragms, establishing the filtration barrier. In Drosophila, nephrocytes show several structural and functional similarities with mammalian podocytes and proximal tubular cells. However, in contrast to podocytes, little is known about the role of apical-basal polarity regulators in these cells. In this study, we used expansion microscopy and found the apical polarity determinants of the PAR/aPKC and Crb-complexes to be predominantly targeted to the cell cortex in proximity to the nephrocyte diaphragm, whereas basolateral regulators also accumulate intracellularly. Knockdown of PAR-complex proteins results in severe endocytosis and nephrocyte diaphragm defects, which is due to impaired aPKC recruitment to the plasma membrane. Similar, downregulation of most basolateral polarity regulators disrupts Nephrin localization but had surprisingly divergent effects on endocytosis. Our findings suggest that morphology and slit diaphragm assembly/maintenance of nephrocytes is regulated by classical apical-basal polarity regulators, which have distinct functions in endocytosis.

Specification of the patterning of a ductal tree during branching morphogenesis of the submandibular gland

The development of ductal structures during branching morphogenesis relies on signals that specify ductal progenitors to set up a pattern for the ductal network. Here, we identify cellular asymmetries defined by the F-actin cytoskeleton and the cell adhesion protein ZO-1 as the earliest determinants of duct specification in the embryonic submandibular gland (SMG). Apical polarity protein aPKCζ is then recruited to the sites of asymmetry in a ZO-1-dependent manner and collaborates with ROCK signaling to set up apical-basal polarity of ductal progenitors and further define the path of duct specification. Moreover, the motor protein myosin IIB, a mediator of mechanical force transmission along actin filaments, becomes localized to vertices linking the apical domains of multiple ductal epithelial cells during the formation of ductal lumens and drives duct maturation. These studies identify cytoskeletal, junctional and polarity proteins as the early determinants of duct specification and the patterning of a ductal tree during branching morphogenesis of the SMG.

Using the Air-Liquid Interface Approach to Foster Apical-Basal Polarization of Mammalian Female Reproductive Tract Epithelia In Vitro.

Oviduct and uterus are key female reproductive organs lined by ciliated simple columnar epithelia, which are the first line of maternal contact with gametes and the developing embryo during reproduction and which warrant the optimal developmental environment for the conceptus. A major challenge for modeling these epithelia in vitro is the preservation of apical-basal polarization and cilia formation. The air-liquid interface (ALI) culture approach is a technology originally invented for modeling epidermal and airway epithelia. It has recently been shown that it also allows the establishment of highly differentiated in vitro models of epithelia that do not have access to ambient air in vivo. In this chapter, we present a comprehensive ALI procedure to model female reproductive tract (FRT) epithelia of different mammalian species in vitro over extended time periods. As a working example, the protocol focuses on primary oviductal epithelial cells (OEC) isolated from domestic pig. Hints on protocol variations for the culture of OEC from other species are provided in the Subheading 4.

Intercellular Regulation of Apical-Basal Polarity Coordinates Tissue Homeostasis and Growth

Intercellular Regulation of Apical-Basal Polarity Coordinates Tissue Homeostasis and Growth

Protein-Functionalized Poly(ethylene glycol) Hydrogels as Scaffolds for Monolayer Organoid Culture.

Stem cell-derived, organotypic in vitro models, known as organoids, have emerged as superior alternatives to traditional cell culture models due to their unparalleled ability to recreate complex physiological and pathophysiological processes. For this reason, they are attractive targets of tissue-engineering efforts, as constructs that include organoid technology would be expected to better simulate the many functions of the desired tissue or organ. While the 3D spheroidal architecture that is the default architecture of most organoid models may be preferred for some applications, 2D monolayer arrangements remain the preferred organization for many applications in tissue engineering. Therefore, in this work, we present a method to create monolayer organoid cultures on poly(ethylene glycol) (PEG) hydrogel scaffolds, using intestinal epithelial organoids (IEOs) as a proof-of-concept. Our process involves two steps: the hydrogel is first functionalized with a layer of poly(D-lysine) (PDL), which then allows the adsorption of pristine, unmodified basement membrane proteins. This approach successfully mediates the formation of IEO monolayer unlike conventional approaches that rely on covalent modification of the hydrogel surface with cell-adhesive peptides and basement membrane proteins. We show that these IEO monolayers recreate important physiological functions of the native intestinal epithelium, including multilineage differentiation, apical-basal polarization, and the ability to model infections with human norovirus. We also show coating of a scaffold mimicking intestinal villous topography, resulting in a 3D IEO monolayer. We expect that this protocol will be useful to researchers attempting to leverage the increased physiological relevance of organoid models to elevate the potential of their tissue-engineered constructs. Impact statement While organoids are physiologically superior models of biological functions than traditional cell cultures, their 3D spheroidal architecture is an obstacle to their incorporation in many tissue-engineering applications, which often prefer 2D monolayer arrangements of cells. For this reason, we developed a protocol to establish monolayer cultures of organoids on poly(ethylene glycol) hydrogels and demonstrate its utility using intestinal epithelial organoids as a proof-of-concept. We expect that this protocol will be of use to researchers creating engineered tissues for both regenerative medicine applications, as well as advanced in vitro experimental models.

PolarProtDb: A Database of Transmembrane and Secreted Proteins showing Apical-Basal Polarity

Most cells in multicellular organisms are somehow asymmetric, polarized: maintaining separate membrane domains. Typical examples are the epithelial cells (apical-basal polarization), neurons (dendritic-axonal domains), or migratory cells (with a leading and a trailing edge). Here we present the most comprehensive database containing experimentally verified mammalian proteins that display polarized sorting or secretion, focusing on epithelial polarity. In addition to the source cells or tissues, homology-based inferences and transmembrane topology (if applicable) are all provided. PolarProtDb also offers a detailed interface displaying all information that may be relevant for trafficking: including post-translational modifications (glycosylations and phosphorylations), known or predicted short linear motifs conserved across orthologs, as well as potential interaction partners. Data on polarized sorting has so far been scattered across myriads of publications, hence difficult to access. This information can help researchers in several areas, such as scanning for potential entry points of viral agents like COVID-19. PolarProtDb shall be a useful resource to design future experiments as well as for comparative analyses. The database is available at http://polarprotdb.enzim.hu.

Polarity Establishment and Maintenance in Ascidian Notochord.

Cell and tissue polarity due to the extracellular signaling and intracellular gene cascades, in turn, signals the directed cell behaviors and asymmetric tissue architectures that play a crucial role in organogenesis and embryogenesis. The notochord is a characteristic midline organ in chordate embryos that supports the body structure and produces positioning signaling. This review summarizes cellular and tissue-level polarities during notochord development in ascidians. At the early stage, planar cell polarity (PCP) is initialized, which drives cell convergence extension and migration to form a rod-like structure. Subsequently, the notochord undergoes a mesenchymal-epithelial transition, becoming an unusual epithelium in which cells have two opposing apical domains facing the extracellular lumen deposited between adjacent notochord cells controlled by apical-basal (AB) polarity. Cytoskeleton distribution is one of the main downstream events of cell polarity. Some cytoskeleton polarity patterns are a consequence of PCP: however, an additional polarized cytoskeleton, together with Rho signaling, might serve as a guide for correct AB polarity initiation in the notochord. In addition, the notochord’s mechanical properties are associated with polarity establishment and transformation, which bridge signaling regulation and tissue mechanical properties that enable the coordinated organogenesis during embryo development.

Bleomycin induced apical-basal polarity loss in alveolar epithelial cell contributes to experimental pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrosing interstitial lung disease with limited therapeutic options and a median survival of 3 years after diagnosis. Dysregulated epithelial regeneration is key event involved in initiating and sustaining IPF. The type II alveolar epithelial cells (AECIIs) play a crucial role for epithelial regeneration and stabilisation of alveoli. Loss of cell apical-basal polarity contributes to fibrosis. AECII has apical-basal polarity, but it is poorly understood whether AECII apical-basal polarity loss is involved in fibrosis. Bleomycin is a traditional inducer of pulmonary fibrosis. Here firstly we observed that bleomycin induced apical-basal polarity loss in cultured AECIIs. Next, cell polarity proteins lethal (2) giant larvae 1 (Lgl1), PAR-3A, aPKC and PAR-6B were investigated. We found bleomycin induced increases of Lgl1 protein and decreases of PAR-3A protein, and bleomycin-induced PAR-3A depression was mediated by increased-Lgl1. Then Lgl1 siRNA was transfected into AECIIs. Lgl1 siRNA prevented apical-basal polarity loss in bleomycin-treated AECIIs. At last, Lgl1-conditional knockout mice were applied in making animal models. Bleomycin induced pulmonary fibrosis, but this was attenuated in Lgl1-conditional knockout mice. Together, these data indicated that bleomycin mediated AECII apical-basal polarity loss which contributed to experimental pulmonary fibrosis. Inhibition of Lgl1 should be a potential therapeutic strategy for the disease.

The Overlapping and Distinct Roles of HAM Family Genes in Arabidopsis Shoot Meristems.

In Arabidopsis shoot apical meristems (SAMs), a well-characterized regulatory loop between WUSCHEL (WUS) and CLAVATA3 (CLV3) maintains stem cell homeostasis by regulating the balance between cell proliferation and cell differentiation. WUS proteins, translated in deep cell layers, move into the overlaying stem cells to activate CLV3. The secreted peptide CLV3 then regulates WUS levels through a ligand-receptor mediated signaling cascade. CLV3 is specifically expressed in the stem cells and repressed in the deep cell layers despite presence of the WUS activator, forming an apical-basal polarity along the axis of the SAM. Previously, we proposed and validated a hypothesis that the HAIRY MERISTEM (HAM) family genes regulate this polarity, keeping the expression of CLV3 off in interior cells of the SAM. However, the specific role of each individual member of the HAM family in this process remains to be elucidated. Combining live imaging and molecular genetics, we have dissected the conserved and distinct functions of different HAM family members in control of CLV3 patterning in the SAMs and in the de novo shoot stem cell niches as well.

Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment.

The crosstalk between tumor cells and the adjacent normal epithelium contributes to cancer progression, but its regulators have remained elusive. Here, we show that breast cancer cells maintained in hypoxia release small extracellular vesicles (sEVs) that activate mitochondrial dynamics, stimulate mitochondrial movements, and promote organelle accumulation at the cortical cytoskeleton in normal mammary epithelial cells. This results in AKT serine/threonine kinase (Akt) activation, membrane focal adhesion turnover, and increased epithelial cell migration. RNA sequencing profiling identified integrin-linked kinase (ILK) as the most upregulated pathway in sEV-treated epithelial cells, and genetic or pharmacologic targeting of ILK reversed mitochondrial reprogramming and suppressed sEV-induced cell movements. In a three-dimensional (3D) model of mammary gland morphogenesis, sEV treatment induced hallmarks of malignant transformation, with deregulated cell death and/or cell proliferation, loss of apical-basal polarity, and appearance of epithelial-to-mesenchymal transition (EMT) markers. Therefore, sEVs released by hypoxic breast cancer cells reprogram mitochondrial dynamics and induce oncogenic changes in a normal mammary epithelium.

Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC.

Apical-basal polarity underpins the formation of epithelial barriers that are crucial for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. Lgl plays a role as an aPKC inhibitor, but it remains unclear whether Lgl also forms complexes with Dlg or Scrib. Using fluorescence recovery after photobleaching, we show that Lgl does not form immobile complexes at the lateral domain of Drosophila follicle cells. Optogenetic depletion of plasma membrane PIP2 or dlg mutants accelerate Lgl cortical dynamics. However, Dlg and Scrib are required only for Lgl localization and dynamic behavior in the presence of aPKC function. Furthermore, light-induced oligomerization of basolateral proteins indicates that Lgl is not part of the Scrib-Dlg complex in the follicular epithelium. Thus, Scrib and Dlg are necessary to repress aPKC activity in the lateral domain but do not provide cortical binding sites for Lgl. Our work therefore highlights that Lgl does not act in a complex but in parallel with Scrib-Dlg to antagonize apical determinants.

Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration.

Scribble (Scrib) and Lethal giant larvae 1 (Lgl1) are conserved polarity proteins that play important roles in different forms of cell polarity. The roles of Scrib and Lgl1 in apical-basal cell polarity have been studied extensively, but little is known about their roles in the cell polarity of migrating cells. Furthermore, the effect of Scrib and Lgl1 interaction on cell polarity is largely unknown. In this study, we show that Scrib, through its leucine-rich repeat domain, forms a complex in vivo with Lgl1. Scrib also forms a complex with myosin II, and Scrib, Lgl1, and myosin II colocalize at the leading edge of migrating cells. The cellular localization and the cytoskeletal association of Scrib and Lgl1 are interdependent, as depletion of either protein affects its counterpart. In addition, depletion of either Scrib or Lgl1 disrupts the cellular localization of myosin II. We show that depletion of either Scrib or Lgl1 affects cell adhesion through the inhibition of focal adhesion disassembly. Finally, we show that Scrib and Lgl1 are required for proper cell polarity of migrating cells. These results provide new insights into the mechanism regulating the cell polarity of migrating cells by Scrib, Lgl1, and myosin II.

Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer

BackgroundCancer subtype switching, which involves unclear cancer cell origin, cell fate decision, and transdifferentiation of cells within a confined tumor microenvironment, remains a major problem in pancreatic cancer (PDA).ResultsBy analyzing PDA subtypes in The Cancer Genome Atlas, we identified that epigenetic silencing of apoptosis-associated tyrosine kinase (AATK) inversely was correlated with mRNA expression and was enriched in the quasi-mesenchymal cancer subtype. By comparing early mouse pancreatic lesions, the non-invasive regions showed AATK co-expression in cells with acinar-to-ductal metaplasia, nuclear VAV1 localization, and cell cycle suppression; but the invasive lesions conversely revealed diminished AATK expression in those with poorly differentiated histology, cytosolic VAV1 localization, and co-expression of p63 and HNF1α. Transiently activated AATK initiates acinar differentiation into a ductal cell fate to establish apical-basal polarization in acinar-to-ductal metaplasia. Silenced AATK and ectopically expressed p63 and HNF1α allow the proliferation of ductal PanINs in mice.ConclusionEpigenetic silencing of AATK regulates the cellular transdifferentiation, proliferation, and cell cycle progression in converting PDA-subtypes.

KLF4 Coordinates Corneal Epithelial Apical-Basal Polarity and Plane of Cell Division and Is Downregulated in Ocular Surface Squamous Neoplasia.

PurposePreviously, we demonstrated that Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) homeostasis by suppressing epithelial-mesenchymal transition (EMT) and TGF-β signaling. As TGF-β affects epithelial apicobasal polarity (ABP) and plane of division, we investigated the role of KLF4 in these processes.Methods Klf4 was ablated in adult ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mouse CE using doxycycline chow. ABP and plane of division markers’ expression in Klf4Δ/ΔCE and human ocular surface squamous neoplasia (OSSN) tissues relative to controls was evaluated by quantitative PCR, immunoblots, and/or immunofluorescent staining.Results Klf4Δ/ΔCE CE cells displayed downregulation of apical Pals1 and Crumbs1, apicolateral Par3, and basolateral Scribble, as well as upregulation of Rho family GTPase Cdc42, suggesting disruption of ABP. Phalloidin staining revealed that the Klf4Δ/ΔCE CE actin cytoskeleton is disrupted. Klf4Δ/ΔCE cells favored vertical plane of division within 67.5° to 90° of the CE basement membrane (39% and 47% of the dividing cells relative to 23% and 26% in the control based on phospho-histone-H3 and survivin, respectively), resulting in more dividing cells within the Klf4Δ/ΔCE CE as reported previously. KLF4 was downregulated in human OSSN tissues that displayed EMT and downregulation of PAR3, PALS1, and SCRIB, consistent with a protective role for KLF4.ConclusionsBy demonstrating that Klf4 ablation affects CE expression of ABP markers and Cdc42, cytoskeletal actin organization, and the plane of cell division and that KLF4 is downregulated in OSSN tissues that display EMT and lack ABP, these results elucidate the key integrative role of KLF4 in coordinating CE cell polarity and plane of division, loss of which results in OSSN.

Par complex cluster formation mediated by phase separation

The evolutionarily conserved Par3/Par6/aPKC complex regulates the polarity establishment of diverse cell types and distinct polarity-driven functions. However, how the Par complex is concentrated beneath the membrane to initiate cell polarization remains unclear. Here we show that the Par complex exhibits cell cycle-dependent condensation in Drosophila neuroblasts, driven by liquid–liquid phase separation. The open conformation of Par3 undergoes autonomous phase separation likely due to its NTD-mediated oligomerization. Par6, via C-terminal tail binding to Par3 PDZ3, can be enriched to Par3 condensates and in return dramatically promote Par3 phase separation. aPKC can also be concentrated to the Par3N/Par6 condensates as a client. Interestingly, activated aPKC can disperse the Par3/Par6 condensates via phosphorylation of Par3. Perturbations of Par3/Par6 phase separation impair the establishment of apical–basal polarity during neuroblast asymmetric divisions and lead to defective lineage development. We propose that phase separation may be a common mechanism for localized cortical condensation of cell polarity complexes.