TY - JOUR. T1 - The Aspergillus nidulans sepA gene encodes an FH1/2 protein involved in cytokinesis and the maintenance of cellular polarity. AU - Harris, Steven D.. AU - Hamer, Lisbeth. AU - Sharpless, Kathryn E.. AU - Hamer, John E.. PY - 1997/6/16. Y1 - 1997/6/16. N2 - Cytokinesis (septation) in the fungus Aspergillus nidulans occurs through the formation of a transient actin ring at the incipient division site. Temperature-sensitive mutations in the sepA gene prevent septation and cause defects in the maintenance of cellular polarity, without affecting growth and nuclear division. The sepA gene encodes a member of the growing family of FH1/2 proteins, which appear to have roles in morphogenesis and cytokinesis in organisms such as yeast and Drosophila. Results from temperature shift and immunofluorescence microscopy experiments strongly suggest that sepA function requires a preceding mitosis and that sepA acts prior to actin ring formation. Deletion mutants of sepA exhibit ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
TY - JOUR. T1 - Chondroitin sulfate proteoglycan 4 regulates zebrafish body axis organization via Wnt/ planar cell polarity pathway. AU - Lee, Yen Hua. AU - Kawakami, Koichi. AU - HuangFu, Wei Chun. AU - Liu, I. Hsuan. PY - 2020/1/1. Y1 - 2020/1/1. N2 - Pericellular and extracellular proteoglycans play an important role in modulating morphogen gradients and signal transductions. Chondroitin sulfate proteoglycan 4 (Cspg4) is a membrane spanning proteoglycan expressed in immature progenitor cells and cancer cells. Cspg4 participates in cellular events such as proliferation, migration and signal transduction, and these events are generally important for embryo development. In this study, we characterized Cspg4 for its roles in zebrafish embryonic development. Our results demonstrated that cspg4 was maternally expressed from 0 to 3 hours post fertilization (hpf) and expressed in the anterior and posterior embryo end after 9 hpf. Knocking-down cspg4 resulted in a shorter anterior-posterior axis than ...
Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell
Cellular polarization is crucial for many biological processes, including cell morphogenesis, proliferation, and differentiation. The orientation of the polarity axis is initially defined by asymmetrical extrinsic or intrinsic cues acting at the cell surface, which then have to be recognized and interpreted by signaling molecules, leading to the asymmetrical activation/inhibition and/or distribution of downstream effectors. This asymmetry is further stabilized by rearrangements of the cytoskeleton, enabling the cell to assume an asymmetric shape (Sohrmann and Peter, 2003).. In pollen tubes, we can consider two distinct axes: the polarity axis and the growth axis. The polarity axis can be drawn transversally at the base of the tip dome separating the tip region from the rest of the tube, whereas the growth axis is perpendicular to the polarity axis and divides the tubes longitudinally (symmetry axis). Despite the fact that pollen tubes are highly polarized cells undergoing polar growth, they have ...
What is the importance of polarity signaling in regulating asymmetric divisions in mammals? In Drosophila neuroblasts, the initial polarization cue comes from the apical enrichment of the polarity proteins Par3, Par6 and aPKC. This apical distribution is essential for asymmetric localization of cell fate determinants, which is coupled to spindle orientation by binding to the adaptor protein Inscuteable (Insc) (Fig. 3A). Insc then recruits a protein complex consisting of the heterotrimeric G protein α1-subunit (Gα1), PINS and MUD, which provides attachment sites for astral microtubules (Knoblich, 2010). Polarized distribution of the aPKC-Par complex is inherited from the epithelial cell, from which the neuroblast arose after delamination (Prehoda, 2009). Similarly, in both mouse neurons and in the epidermis, PAR3 and aPKC show an apical distribution that is independent of cell division (Lechler and Fuchs, 2005). In the epidermis, this apical polarity might have been inherited from the polarized ...
Proper spatial and temporal specification of cells during development is crucial for the generation of cellular diversity in the nervous system of complex organisms. We are interested in the mechanisms underlying the establishment of cellular polarity and the generation of neuronal cell lineages during neurulation in Danio rerio. We were able to show that neurulation in zebrafish embryos is characterised by oriented cell divisions and the progressive establishment of cellular polarity. Mitoses in the neural plate and neural tube are planar, but in the neural keel/rod stage the mitotic spindle rotates by 90°, causing cell divisions to occur perpendicular to the plane of the neuroepithelium. However, the mechanisms and molecules that establish cellular polarity and cause the stereotypic orientation of the mitotic spindle during neurulation are still largely unknown. In order to address this topic, we are currently analyzing the putative cell fate determinant Numb and the role of the ...
Involved in the planar cell polarity (PCP) pathway that is essential for the polarization of epithelial cells during morphogenetic processes, including gastrulation and neurulation (By similarity). PCP is maintained by two molecular modules, the global and the core modules, PRICKLE3 being part of the core module (By similarity). Distinct complexes of the core module segregate to opposite sides of the cell, where they interact with the opposite complex in the neighboring cell at or near the adherents junctions (By similarity). Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity).
Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level. We have built an in-silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila. We have carried out a systematic comparison of in-silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct
These studies suggest a non-cell-autonomous role for Vangl2-PCP signaling in coronary artery formation. The coronary vessels in Lp/Lp hearts fail to develop a normal SMC layer and enlarged ectopic vessels are found in the subepicardium, on the surface of the heart. Loss of functional Vangl2 results in reduced deposition of fibronectin in the subepicardial space, which may limit normal migration of EPDCs into the myocardium. In addition activation of RhoA/ROCK signaling in the myocardium is disrupted, which causes disorganization within the ventricular wall via effects on the cytoskeleton. Although the precise mechanism by which PCP signaling regulates cytoskeletal organization remains unclear, mislocalization of activated MYPT is likely to have major implications for polarization and organization of ventricular cardiomyocytes. These data suggest that PCP signaling may be important at a number of levels for development of the mature ventricular myocardium and coronary vessels.. Proper ...
The exon junction complex regulates the cell polarity determinant Discs large 1, which acts independently from its role in cell polarity to protect Dishevelled protein from lysosomal degradation in Wingless/Wnt signaling.
Mutations in the C. elegans gene egl-27 cause defects in cell polarity and cell migration: the polarity of the asymmetric T cell division is disrupted and the descendants of the migratory QL neuroblast migrate incorrectly because they fail to express the Hox gene mab-5. Both of these processes are known to be controlled by Wnt pathways. Mosaic analysis indicates that egl-27 function is required in the T cell for proper cell polarity. We cloned egl-27 and discovered that a domain of the predicted EGL-27 protein has similarity to Mta1, a mammalian factor overexpressed in metastatic cells. Overlaps in the phenotypes of egl-27 and Wnt pathway mutants suggest that the EGL-27 protein interacts with Wnt signaling pathways in C. elegans.. ...
Background-Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results-Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for ...
TY - JOUR. T1 - Brefeldin A rapidly disrupts plasma membrane polarity by blocking polar sorting in common endosomes of MDCK cells. AU - Wang, E.. AU - Pennington, J. G.. AU - Goldenring, J. R.. AU - Hunziker, W.. AU - Dunn, Kenneth. PY - 2001. Y1 - 2001. N2 - Recent studies showing thorough intermixing of apical and basolateral endosomes have demonstrated that endocytic sorting is critical to maintaining the plasma membrane polarity of epithelial cells. Our studies of living, polarized cells show that disrupting endocytosis with brefeldin-A rapidly destroys the polarity of transferrin receptors in MDCK cells while having no effect on tight junctions. Brefeldin-A treatment induces tubulation of endosomes, but the sequential compartments and transport steps of the transcytotic pathway remain intact. Transferrin is sorted from LDL, but is then missorted from common endosomes to the apical recycling endosome, as identified by its nearly neutral pH, and association with GFP chimeras of Rabs 11a and ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic ...
Establishing and maintaining epithelial cell polarity is essential for animal development and physiology. Epithelia are sheets of adherent cells that form our skin and line our organs. Each side of an epithelium has distinct molecular properties to engage the extracellular environments on either side of the sheet. Similarly to all polarized cells, apical-basal epithelial cell polarity is established and maintained by cortical landmarks (reviewed by Nelson, 2003; Suzuki and Ohno, 2006; Goldstein and Macara, 2007; St Johnston and Ahringer, 2010). Defining how these landmarks are positioned and how they organize the cell is essential for understanding epithelial cell polarity.. Bazooka (Baz/PAR-3) forms apical polarity landmarks in epithelial cells. In MDCK cells, PAR-3 is important for assembling and maintaining tight junctions and adherens junctions (Chen and Macara, 2005; Ooshio et al., 2007). In C. elegans, PAR-3 has been shown to direct adherens junction assembly during intestinal development ...
Polarized light has vibrations occurring within them in one plane. On the other hand, unpolarized light has vibrations occurring within them randomly angles with no plane.. In a Polarized light, a process which evolves during this stage can help to transform the light into polarized that originally remains unpolarized and has the title of polarization. Note that its possible to alter unpolarized light into an energized light and the process is called polarization.. This is quite not exactly like what you may see in case you somehow managed to look together with a silent and watch a constant wave moving towards you. According to quantum mechanics, electromagnetic waves may similarly be flooding of particles known as photons. A photon has one of two possible twists; it could either turn in a right-hand sense or a left-hand sense about its path of travel.. ...
How is the polarity of epithelial cells established and maintained?. Epithelial cells constitute the most widespread and evolutionarily ancient mode of animal tissue organization. The functions of epithelia rely on their highly polarized architecture, in which specific proteins are restricted to apical, junctional, and basolateral surfaces. We are working to understand the mechanisms that regulate cell polarity, exploiting our discovery of the Scribble module that acts to distinguish the epithelial basolateral domain by antagonizing the apical Par/aPKC complex. Cell biological assays of protein trafficking and biochemical studies of Scribble module partners are revealing their mysterious basic polarizing activities. As novel insights can come from unbiased genetic screens, we have designed several to isolate new regulators of epithelial polarity. These screens identify genes that directly interface with the conserved polarity regulators, revealing mechanistic links with basic membrane ...
Genetics and biochemistry have been used to map many of the individual pathways that establish and maintain cell polarity in yeast, but Drees et al. (page 549) have now produced the equivalent of an aerial photograph of these processes. Using a high-throughput yeast two-hybrid screen, the authors assayed the universe of likely protein-protein interactions involved in cell polarity development. The resulting protein interaction map provides tantalizing insights and identifies dozens of potential mechanistic connections worth closer examination.. The authors used 68 yeast proteins associated with the actin cytoskeleton, septins, the secretory apparatus, and Rho-type GTPases as baits in parallel two-hybrid screens covering ∼90% of the predicted Saccharomyces cerevisiae ORFs. The screen uncovered 128 novel protein-protein interactions, including 44 involving previously uncharacterized proteins. The appearance of known interactions in the screen, along with subcellular localization studies, ...
The Glued gene of Drosophila melanogaster encodes the homologue of the vertebrate p150Glued subunit of dynactin. The Glued1 mutation compromises the dynein-dynactin retrograde motor complex and causes disruptions to the adult eye and the CNS, including sensory neurons and the formation of the giant fiber system neural circuit. We performed a 2-stage genetic screen to identify mutations that modified phenotypes caused by over-expression of a dominant-negative Glued protein. We screened over 34,000 flies and isolated 41 mutations that enhanced or suppressed an eye phenotype. Of these, 12 were assayed for interactions in the giant fiber system by which they altered a giant fiber morphological phenotype and/or altered synaptic function between the giant fiber and the tergotrochanteral muscle motorneuron. Six showed interactions including a new allele of atypical protein kinase C (aPKC). We show that this cell polarity regulator interacts with Glued during central synapse formation. We have mapped the five
Cell polarity - the morphological and functional differentiation of cellular compartments in a directional manner - is required for processes such as orientation of cell division, directed cellular growth and motility. How the interplay of components within the complexity of a cell leads to cell polarity is still heavily debated. In this Review, we focus on one specific aspect of cell polarity: the non-uniform accumulation of proteins on the cell membrane. In cells, this is achieved through reaction-diffusion and/or cytoskeleton-based mechanisms. In reaction-diffusion systems, components are transformed into each other by chemical reactions and are moving through space by diffusion. In cytoskeleton-based processes, cellular components (i.e. proteins) are actively transported by microtubules (MTs) and actin filaments to specific locations in the cell. We examine how minimal systems - in vitro reconstitutions of a particular cellular function with a minimal number of components - are designed, how ...
The leading edge two regions hdlg-13 and insertion 12, both unique and partially redundant functions in two regions of alternative splicing the human homolog of the Drosophila Discs-large tumor suppressor. In adult flies, is located at the apical-lateral membrane boundary, isoform S97 expression is localized to the cell borders, coexpressed with scrib, at the septate junction and within the CNS of both embryos and larvae (in non-neural and neural cells) and are only the characteristics of malignant cancers derived from epithelial tissues. Loss of either Stardust [Sdt] or Dlg affects epithelial development, assembling Crumbs [Crb] homologs among MPP family members of Drosoplila sdt. Self-refinement of Notch activity through the transmembrane protein Crumbs: modulation have been implicated in the specification of tissue boundaries, in the Drosophila wing imaginal disc, Crumbs is involved in a feedback mechanism used by the Notch polarity determinant. In the control of both apico-basal polarity and ...
Heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) determine tissue and cell polarity in a variety of organisms. In yeast, cells orient polarized growth toward the mating partner along a pheromone gradient by a mechanism that requires Far1p and Cdc24p. Far1p bound Gβγ and interacted with polarity establishment proteins, which organize the actin cytoskeleton. Cells containing mutated Far1p unable to bind Gβγ or polarity establishment proteins were defective for orienting growth toward their mating partner. In response to pheromones, Far1p moves from the nucleus to the cytoplasm. Thus, Far1p functions as an adaptor that recruits polarity establishment proteins to the site of extracellular signaling marked by Gβγ to polarize assembly of the cytoskeleton in a morphogenetic gradient. ...
One unique aspect of VEGFR2 endocytosis is its regulation by several transmembrane and cytosolic interacting proteins, which play a role in either VEGFR2 internalization or degradation. A group of such proteins involved in VEGFR2 internalization is Dab2, ephrin-B2, and PAR-3. Dab2,46 a clathrin-associated sorting protein, and the cell polarity regulator PAR-3 interact with the transmembrane protein ephrin-B2 and VEGFR2. Disruption of this interaction by silencing of Dab2 or PAR-3 causes reduced VEGFR2 internalization and impaired VEGF-induced angiogenesis. After RTKs are internalized into early endosomes, a proportion of the receptors is modified by ubiquitin and then sorted for lysosomal degradation. CCM347 and myoferlin,48 respectively, associate with VEGFR2 in ECs and serve to enhance VEGFR2 stability by preventing receptor degradation.. Apart from internalization and degradation, VEGFR2 signaling is regulated by protein tyrosine phosphatases (PTPs), such as VE-PTP and PTP1b. VE-PTP is a ...
The asymmetric localization of planar cell polarity (PCP) proteins is essential for the establishment of many planar polarized cellular processes, but the mechanisms that maintain these asymmetric distributions remain poorly understood. A body of evidence has tied oriented subapical microtubules (MTs) to the establishment of PCP protein polarity, yet recent studies have suggested that the MT cytoskeleton is later dispensable for the maintenance of this asymmetry. As MTs underlie the vesicular trafficking of membrane-bound proteins within cells, the requirement for MTs in the maintenance of PCP merited further investigation. I sought to investigate the complex interactions between PCP proteins and the MT cytoskeleton in the polarized context of the floorplate of the zebrafish neural tube. We demonstrated that the progressive posterior polarization of the primary cilia of floorplate cells requires not only Vangl2 but also Fzd3a. I determined that GFP-Vangl2 asymmetrically localizes to anterior ...
Cell polarity factors positioned at the cell tips provide spatial cues to limit Cdr2 distribution to the cell middle. In fission yeast Schizosaccharomyces pombe (S. Pombe), cells divide at a defined, reproducible size during mitosis because of the regulated activity of Cdk1.[8] The cell polarity protein kinase Pom1, a member of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) family of kinases, localizes to cell ends. In Pom1 knockout cells, Cdr2 was no longer restricted to the cell middle, but was seen diffusely through half of the cell. From this data it becomes apparent that Pom1 provides inhibitory signals that confine Cdr2 to the middle of the cell. It has been further shown that Pom1-dependent signals lead to the phosphorylation of Cdr2. Pom1 knockout cells were also shown to divide at a smaller size than wild-type, which indicates a premature entry into mitosis.[7] Pom1 forms polar gradients that peak at cell ends, which shows a direct link between size control ...
The asymmetric distribution of membrane proteins along the apical to basal axis of a simple epithelial cell ensures that epithelial barrier and transport functions are properly regulated. However, apico-basal polarity means something different in a multi-layered epithelium such as the epidermis. This tissue provides essential protection against water loss, mechanical stress, and other environmental insults. These functions require that architectural features be polarized along the entire apical to basal axis (i.e. superficial to deep layers) of the stratified epithelium, not just within an individual cell. How information embedded within this polarized architecture is translated to generate a functional epidermis is poorly understood.. While canonical polarity proteins such as Par3/5 and aPKC have been established to play important roles in the epidermis, the contributions of other highly patterned membrane proteins to tissue polarity are poorly understood. Among the most highly polarized ...
Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminals, to cilia, to nonpolarized cell surfaces or to epithelial cell basolateral membranes, thus taking part in the establishment of cellular polarity. We report here the consequences of kinesin 2 motor inactivation in the thyroid of 3-week-old Kif3a(Δ)(/flox) Pax8(Cre/)(+) mutant mice. Our results indicate first that 3-week-old Pax8(Cre/)(+) mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood thyroxine levels in the normal range ...
Despite decades of research there are still basic aspects of planar cell polarity that are not well understood. Recent work in mouse tracheal epithelial cells links microtubules with both establishing asymmetry as well as responding to this asymmetry to coordinate cellular orientation ...
Planar cell polarity (PCP) describes the polarization of cells within the plane of a tissue and is an essential feature of embryonic morphogenesis. Disruption o...
Complete information for PRICKLE2 gene (Protein Coding), Prickle Planar Cell Polarity Protein 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The virologic synapse (VS), which is formed between a virus-infected and uninfected cell, plays a central role in the transmission of certain viruses, such as HIV and HTLV-1. During VS formation, HTLV-1-infected T-cells polarize cellular and viral proteins toward the uninfected T-cell. This polarization resembles anterior-posterior cell polarity induced by immunological synapse (IS) formation, which is more extensively characterized than VS formation and occurs when a T-cell interacts with an antigen-presenting cell. One measure of cell polarity induced by both IS or VS formation is the repositioning of the microtubule organizing center (MTOC) relative to the contact point with the interacting cell. Here we describe an automated, high throughput system to score repositioning of the MTOC and thereby cell polarity establishment. The method rapidly and accurately calculates the angle between the MTOC and the IS for thousands of cells. We also show that the system can be adapted to score anterior-posterior
Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent
The coordination of cell polarity within the plane of the tissue layer (planar polarity) is crucial for the development of diverse multicellular organisms. Small Rac/Rho-family GTPases and the actin cytoskeleton contribute to planar polarity formation at sites of polarity establishment in animals and plants. Yet, upstream pathways coordinating planar polarity differ strikingly between kingdoms. In the root of Arabidopsis thaliana, a concentration gradient of the phytohormone auxin coordinates polar recruitment of Rho-of-plant (ROP) to sites of polar epidermal hair initiation. However, little is known about cytoskeletal components and interactions that contribute to this planar polarity or about their relation to the patterning machinery. Here, we show that ACTIN7 (ACT7) represents a main actin isoform required for planar polarity of root hair positioning, interacting with the negative modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2). ACT7, AIP1-2 and their genetic interaction are required for ...
Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster ...
I am interested in cellular and molecular mechanisms underlying co-ordinated and directional cell movements. The primary focus is on morphogenetic movements occurring during gastrualtion using the zebrafish as a model system; epiboly, convergence/extension and anterior migration of mesodermal cells. Since we showed that Wnt11 is an important regulator of convergence/extension movements during gastrulation in vertebrates, it has been evident that this ligand acts in a pathway related to the planar cell polarity (PCP) pathway in Drosophila. Recently, the core PCP genes have been also implicated in regulating a variety of morphogenetic processes in vertebrates including neural tube closure, orientation of cochlear hair cells, migration of facial motorneurons and ciliogenesis. Current projects are a) Understanding mechanisms by which core PCP proteins regulate gastrulation movements in zebrafish; b) Identifying and characterising genetic pathways that act in or in parallel with the PCP pathway ...
In all organisms, cell polarity is fundamental for most aspects of cell physiology. In many species and cell types, it is controlled by the evolutionarily conserved PAR-3, PAR-6 and aPKC proteins, which are asymmetrically localized at the cell cortex where they define specific domains. While PAR proteins define the antero-posterior axis of the early C. elegans embryo, the mechanism controlling their asymmetric localization is not fully understood. Here we studied the role of endocytic regulators in embryonic polarization and asymmetric division. We found that depleting the early endosome regulator RAB-5 results in polarity-related phenotypes in the early embryo. Using Total Internal Reflection Fluorescence (TIRF) microscopy, we observed that PAR-6 is localized at the cell cortex in highly dynamic puncta and depleting RAB-5 decreased PAR-6 cortical dynamics during the polarity maintenance phase. Depletion of RAB-5 also increased PAR-6 association with clathrin heavy chain (CHC-1) and this ...
Figure 3. The CeAJ and cell-cell adhesion. (A) Schematic representation of known components CeAJ components. Like in vertebrates and Drosophila, C. elegans epithelial cells contain two adhesion complexes, the cadherin-catenin (CCC) and the DLG-1/AJM-1 (DAC) complexes. C. elegans is unique in three respects: (i) there is a single electron-dense area in the CeAJ (see Figure 1B); (ii) LET-413 does not colocalize with DLG-1 (as its homologue Scribble in Drosophila); (iii) PAR-3, PAR-6, PKC-3 and CRB-1 are present at the apical membrane in tubular organs (the existence of apical polarity determinants in epidermal cells is an open question). CeAJs from different epithelia contain the same set of proteins; notable differences concern the identity of the classical claudin-like protein (CLC-1 present in the pharynx, vulva and spermatheca; CLC-2 present in the lateral epidermis). The DAC complex might correspond to the electron-density in the CeAJ. Indeed, immunogold staining experiments localize AJM-1 at ...
The directed orientation of T cell signaling molecules and associated membrane rafts towards a chemokine gradient or a contact point with antigen presenting cell.
We then considered that increased cell death might explain the reduced number of RPCs and neurons observed at E13.5, but staining for activated caspase-3 at E11.5 and E13.5 revealed no significant changes in cell death (E13.5: control, 2.4 ± 1.3 cells/200 μm, n = 4; cDKO, 3.2 ± 1.1 cells/200 μm, n = 4). At E16.5 and P0, however, we found an important increase in the number of caspase-positive cells in cDKO compared with controls (data not shown). Intriguingly, we noticed that the timing of appearance of dead cells in cDKO correlates with the appearance of a dysmorphic retinal neuroepithelium. At E13.5, the cDKO retinas are normally layered and display the expected apical staining of the polarity proteins Par-3 and atypical PKC (data not shown). In addition, there are no ectopic RPC mitoses at E13.5. As seen with PH3 staining, all mitoses appear at the apical surface (Fig. 2D,E). Since the increased cell death and disrupted neuroepithelium polarity are observed after the initial reduction of ...
We first tested no matter whether unpolarized HL-60 neutrophils can break their morphological symmetry and start off to migrate when they are stimulated by a
PARD3 is thought to be a master regulator of apical-basal cell polarity, a process that has been indirectly implicated in tumorigenesis (15, 16). Recently, SCRIB (also known as Scribble) was proposed as a tumor suppressor by virtue of its mislocalization in human breast cancers (17). However, inactivating mutations in SCRIB have not been identified, and it is possible that mutational inactivation of PARD3 (and potentially other polarity complex family members) provides a genetic mechanism that explains dysregulation of cell polarity in a subset of human cancers. While this article was in preparation, Zen and colleagues (18) reported finding PARD3 deletions in the SCCE cell lines also described here (e.g., KYSE-30 and KYSE-270). As shown in our two studies, loss of PARD3 in SCCE cells leads to abnormal cellular contacts, consistent with disruption of the PAR polarity complex. The apparent tissue specificity of PARD3 deletions uncovered in our study, affecting both diverse squamous epithelial ...
Neural Morphogenesis. We study patterning and biomechanics of convergent extension in the neural plate, and the mechanisms of neural tube closure. What cell behaviors shape the neural plate and how are they regulated by midline-originating signals? Mesodermal Morphogenesis. We are interested in the biomechanical role of such molecules as integrin, fibrillin, and cadherins during convergence and extension of the mesoderm. How do molecular components such as these and others such as members of the planar cell polarity pathway drive or guide convergence and extension and axis elongation? Comparative Morphogenesis. We are interested in understanding the variation among species in the mechanisms and biomechanics of gastrulation. This include the mechanisms by which surface mesoderm is removed during gastrulation and neurulation, and the degree to which the embryo uses convergent extension, mesendoderm migration, and Winklebauer rotation to drive gastrulation ...
Epithelial cells display distinct apical and basolateral membrane domains, and maintenance of this asymmetry is essential to the function of epithelial tissues. Polarized delivery of apical and basolateral membrane proteins from the trans Golgi network (TGN) and/or endosomes to the correct domain requires specific cytoplasmic machinery to control the sorting, budding and fission of vesicles. However, the molecular machinery that regulates polarized delivery of apical proteins remains poorly understood. In this study, we show that the small guanosine triphosphatase Rab14 is involved in the apical targeting pathway. Using yeast two-hybrid analysis and glutathione S-transferase pull down, we show that Rab14 interacts with apical membrane proteins and localizes to the TGN and apical endosomes. Overexpression of the GDP mutant form of Rab14 (S25N) induces an enlargement of the TGN and vesicle accumulation around Golgi membranes. Moreover, expression of Rab14-S25N results in mislocalization of the ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Signals emanating from polarity determinants, such as the Crumbs/Amot complex, processes such as mechanotransduction that act through the actin cytoskeleton and mediators of cell density sensing, all can control Yap localization (Genevet & Tapon, 2011; Boggiano & Fehon, 2012; Schroeder & Halder, 2012). In general, these signals flow to the Mst/Lats kinase cassette, and while Mst1/2‐independent Yap phosphorylation has been reported (Yu et al, 2012, 2013; Zhao et al, 2012; Kim et al, 2013), there appears to be a more ubiquitous requirement for Lats. Our data demonstrate that βPix functions at the level of Lats, consistent with the notion that βPix acts in the Hippo pathway downstream of multiple cues. Accordingly, we observed a requirement for βPix in regulating Yap activity in response to cell-cell contact and cell density, actin cytoskeleton disruption and in attachment/detachment events. In all the cases, loss of βPix expression resulted in retention of Yap/Taz in the nucleus and ...
This chapter will take up two types of bipolar items in Japanese to identify various factors that contribute to polarity sensitivity. It has been well known since Fauconnier (1975) that scalar semantics is closely related to licensing of negative polarity items. There are indeed languages like Dutch and Hindi that have negative polarity items overtly marked with a scalar focus particle. The chapter show that there are other morphological characteristics that play important roles in polarity sensitivity. Furthermore, the chapter suggest that the relation between negative concord and negative polarity must be taken into account when concord items and polarity items are morphologically very similar.
TY - JOUR. T1 - Absence of transepithelial anion exchange by rabbit OMCD. T2 - Evidence against reversal of cell polarity. AU - Hayashi, M.. AU - Schuster, V. L.. AU - Stokes, J. B.. PY - 1988. Y1 - 1988. N2 - In the rabbit cortical collecting duct (CCD), Cl tracer crosses the epithelium predominantly via an anion exchange system that operates in either a Cl-Cl or Cl-HCO3 exchange mode. In the present study, we used the 36Cl lumen-to-bath rate coefficient (K(Cl), nm/s), a sensitive measurement of CCD transepithelial anion transport, to investigate the nature of Cl transport in the medullary collecting duct dissected from inner stripe, outer medulla (OMCD). The K(Cl) in OMCD perfused and bathed in HCO3-Ringer solution was low (46.2 ± 8.5 nm/s) and similar to that value observed in the CCD when anion exchange is inhibited and Cl permeates the epithelium by diffusion. Unlike K(Cl) in CCD, K(Cl) in OMCD was not stimulated by adenosine 3,5-cyclic monophosphate (cAMP). OMCD K(Cl) was not altered by ...
This advanced course covers cell polarity and cytoskeletal dynamics emphasizing current literature. For each topic, the course examines (1) the proteins involved, (2) their interactions and regulation, and (3) how they organize specific cellular structures. The coordination of these complexes for orchestrating complex cellular processes is also addressed. These important topics of cell biology are pursued with question-driven lectures, and both round-table discussions and group presentations of research papers.. ...