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| Open AccessMouse embryo geometry drives formation of robust signaling gradients through receptor localization
How receptor localization affects morphogen gradient formation during embryonic development is unclear. Here, the authors study the relationship between the BMP gradient, receptor localization, and compartmentalized geometry in the early mouse embryo, using experimental data and computational simulation.
- Zhechun Zhang
- , Steven Zwick
- & Sharad Ramanathan
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Article
| Open AccessPCP and Wnt pathway components act in parallel during zebrafish mechanosensory hair cell orientation
Planar cell polarity (PCP) regulates hair cell orientation in the zebrafish lateral line. Here, the authors show that mutating Wnt pathway genes (wnt11f1, fzd7a/b, and gpc4) causes concentric hair cell patterns not regulated by PCP, thus showing PCP/Wnt pathway genes have different consequences on hair cell orientation.
- Joaquin Navajas Acedo
- , Matthew G. Voas
- & Tatjana Piotrowski
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Article
| Open AccessPolarity signaling ensures epidermal homeostasis by coupling cellular mechanics and genomic integrity
Many developing tissues require Par-driven polarization, but its role in mammalian tissue maintenance is unclear. Here, the authors show that in mouse epidermis, Par3 governs tissue homeostasis not via orientation of cell division but by coupling cell mechanics with mitotic accuracy and genome integrity.
- Martim Dias Gomes
- , Soriba Letzian
- & Sandra Iden
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Article
| Open AccessLive cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.
- Karl E. Bauer
- , Inmaculada Segura
- & Michael A. Kiebler
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Article
| Open AccessAtypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility
Centrosomes function in cell migration by organizing microtubules. Here, Luo et al. surprisingly show that centrosome proteins also control migration after recruitment by Wnt-PCP proteins to the cell cortex, leading to actin remodelling and protrusive activity relevant to aggressive cancer motility.
- Yi Luo
- , Miriam Barrios-Rodiles
- & Laurence Pelletier
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Article
| Open AccessA MST1–FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis
Angiogenesis is driven by the directed migration of tip endothelial cells towards hypoxic tissues. Here, Kim et al. show that the generation of reactive oxygen species in endothelial cells upon hypoxia activates MST1, which subsequently promotes the nuclear translocation of FOXO1, and thus activates a pro-migratory transcriptional programme in endothelial tip cells.
- Yoo Hyung Kim
- , Jeongwoon Choi
- & Gou Young Koh
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Article
| Open AccessCellular geometry scaling ensures robust division site positioning
Cells divide within a given size range and can scale across differing cell sizes but mechanisms and function remain unclear. Here the authors show, despite the current dogma of fission yeast maintaining constant width, some fission yeast can scale their width and length, impacting the positioning of the cell division site.
- Ying Gu
- & Snezhana Oliferenko
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Article
| Open AccessActo-myosin force organization modulates centriole separation and PLK4 recruitment to ensure centriole fidelity
Centriolar separation is thought to be crucial for centriole duplication, but the mechanism behind separation is poorly understood. Here, using micropatterning, the authors report that actomyosin forces influence the direction, distance, and time of centriole separation.
- Elisa Vitiello
- , Philippe Moreau
- & Martial Balland
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Article
| Open AccessaPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA-binding ability
The cell polarity regulator aPKC is associated with cell proliferation but the precise mechanism are unknown. Here, the authors find that aPKC lambda phosphorylates the FoxO1 transcription factor, a gatekeeper of endothelial growth, during both angiogenesis and angiosarcomas.
- Meghan Riddell
- , Akiko Nakayama
- & Masanori Nakayama
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Article
| Open AccessThe phospholipid PI(3,4)P2 is an apical identity determinant
During de novo establishment of apical-basal polarity, a basolateral membrane must be converted into an apical delivery zone. Here, the authors use MDCK 3D cysts to uncover that the phospholipid PI(3,4)P2 is an apical membrane determinant.
- Álvaro Román-Fernández
- , Julie Roignot
- & David M. Bryant
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Article
| Open AccessEpithelial cells release adenosine to promote local TNF production in response to polarity disruption
Epithelial stress can disrupt polarity and activate TNF and JNK signalling that contributes to inflammation and cell damage. Here, the authors show that disruption of apico-basal polarity leads to adenosine release, activating TNF and JNK and driving an inflammatory response during chronic stress.
- Ingrid Poernbacher
- & Jean-Paul Vincent
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Article
| Open AccessThe last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts
The highly proliferative neuroblasts of the Drosophila larval brain divide over many cell cycles in a polarized manner. Here the authors show that the orientation of the axis of NB divisions is defined by the position of their last-born daughter cell.
- Nicolas Loyer
- & Jens Januschke
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Article
| Open AccessSynchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus
Tracheal development arises due to tube morphogenesis but how this is regulated is unclear. Here, the authors identify polarization of smooth muscle progenitors as controlling murine tracheal development, activating noncanonical Wnt signaling followed by subepithelial morphogenesis and ring cartilage development.
- Keishi Kishimoto
- , Masaru Tamura
- & Mitsuru Morimoto
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Article
| Open AccessThe REN4 rheostat dynamically coordinates the apical and lateral domains of Arabidopsis pollen tubes
Polar growth of pollen tubes is established by polar localization of ROP1 GTPase activity at the apical tip. Here, Li et al. identify REN4 as a ROP1 interaction partner that restrains the ROP1 distribution to the apex by promoting ROP1 endocytosis from lateral domains of the pollen tube membrane.
- Hui Li
- , Nan Luo
- & Zhenbiao Yang
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Article
| Open AccessSTEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap
The perinuclear actin cap determines nuclear morphology but its regulation is currently poorly understood. Here, the authors find that an activator of the Rac1 GTPase, STEF/TIAM2, localises to the nuclear envelope and contributes to perinuclear actin and myosin tension, which in turn regulates the actin cap.
- Anna Woroniuk
- , Andrew Porter
- & Angeliki Malliri
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Article
| Open AccessGon4l regulates notochord boundary formation and cell polarity underlying axis extension by repressing adhesion genes
Anteroposterior axis extension during gastrulation is dynamically coordinated, but how this is regulated at a molecular level is unclear. Here, the authors show in zebrafish that the chromatin factor Gon4l, encoded by ugly duckling, coordinates axis extension by modulating EpCAM and Integrinα3b expression.
- Margot L. K. Williams
- , Atsushi Sawada
- & Lilianna Solnica-Krezel
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Article
| Open AccessSingle cell polarity in liquid phase facilitates tumour metastasis
Polarisation of metastasising cancer cells in circulation has not been investigated before. Here the authors identify single cell polarity as a distinct polarisation state of single cells in liquid phase, and show that perturbing single cell polarity affects attachment, adhesion, transmigration and metastasis in vitro and in vivo.
- Anna Lorentzen
- , Paul F. Becker
- & Mathias Heikenwalder
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Article
| Open AccessBasal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division
Polarized localization of Numb and Pon in Drosophila neuroblasts (NBs) enables their unequal segregation during asymmetric cell divisions. Here, the authors demonstrate liquid-liquid phase separation of Pon and Numb in NBs mediated by multivalent intermolecular interactions is required for their basal condensation.
- Zelin Shan
- , Yuting Tu
- & Wenyu Wen
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Article
| Open AccessExocytosis-coordinated mechanisms for tip growth underlie pollen tube growth guidance
Tip-growing cells can find their growing path toward the source of attractive signals. Here, using experimental data and mathematical modeling, Luo et al. demonstrate that tip-localized exocytosis can integrate guidance cues with Rho GTPase signaling to control cell wall mechanics and direct tip growth in Arabidopsis pollen tubes.
- Nan Luo
- , An Yan
- & Zhenbiao Yang
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Article
| Open AccessPumilio-dependent localization of mRNAs at the cell front coordinates multiple pathways required for chemotaxis
Chemotaxis during differentiation of Dictyostelium discoideum requires four signalling pathways to maintain directional cell migration, but it is unclear how they are coordinated. Here the authors show that the RNA-binding protein Pumilio localizes mRNAs and proteins of these pathways and actin at the cell front during dynamic cell migration.
- Manuel Hotz
- & W. James Nelson
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Article
| Open AccessActomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse embryo
The molecular trigger that establishes cell polarity in the mammalian embryo is unclear. Here, the authors show that de novo polarisation of the mouse embryo at the 8-cell stage is directed by Phospholipase C and Protein kinase C and occurs in two phases: polarisation of actomyosin followed by the Par complex.
- Meng Zhu
- , Chuen Yan Leung
- & Magdalena Zernicka-Goetz
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Article
| Open AccessA Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis
Platelets derive from large precursor cells (megakaryocytes) in the bone marrow. Düttinget al. show that megakaryocyte polarization and platelet biogenesis in the bone-marrow sinusoids are directed by adhesion receptor GPIb signalling and resulting balanced antagonism between RhoA (stop-signal) and Cdc42 (go-signal).
- Sebastian Dütting
- , Frederique Gaits-Iacovoni
- & Bernhard Nieswandt
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Article
| Open AccessThe signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis
It is unclear if there is an interaction between apical-basal (AB) polarity and planar cell polarity (PCP) pathways during morphogenesis. Here, the authors define a role for the melanoma cell adhesion molecule (MCAM), known to regulate PCP, in AB polarity via FGF signallingin vitroand in zebrafish.
- Qian Gao
- , Junfeng Zhang
- & Xiyun Yan
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Article
| Open AccessAn apicobasal gradient of Rac activity determines protrusion form and position
Polarized epithelial cells must correctly position a wide range of subcellular structures. Here the authors demonstrate an apicobasal gradient of Rac GTPase activity, which is maintained by polarity proteins inDrosophilaepithelial sheets, and is required to maintain actin-dependent protrusion form and position.
- Africa Couto
- , Natalie Ann Mack
- & Marios Georgiou
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Article
| Open AccessDistinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte
Asymmetric nuclear positioning in the fruit fly oocyte is essential for the correct localization of axis determinants. Here, the authors show that different microtubule-dependent mechanisms contribute to nuclear transport and ensure the robustness of nuclear positioning.
- Nicolas Tissot
- , Jean-Antoine Lepesant
- & Antoine Guichet
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Article
| Open AccessThe Par3 polarity protein is an exocyst receptor essential for mammary cell survival
The exocyst delivers basolateral proteins from the secretory pathway to the plasma membrane of epithelial cells close to tight junctions. Here the authors show that Par3 acts as a docking site for the exocyst to regulate polarized delivery of basolateral proteins and this is essential to prevent apoptosis and promote mammary cell survival.
- Syed Mukhtar Ahmed
- & Ian G. Macara
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Article
| Open AccessOrthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes
The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.
- Xianpeng Liu
- , Bo Zhao
- & Hiroaki Kiyokawa
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Article
| Open AccessCingulin and actin mediate midbody-dependent apical lumen formation during polarization of epithelial cells
Polarisation of epithelial cells causes lumen formation, which is mediated by apical membrane initiation site (AMIS) and FIP5, but how this is regulated is unclear. Here, the authors identify cingulin as a FIP-5 interacting protein, recruiting the Rac1-WAVE/Scar complex to the AMIS and branched actin formation.
- Anthony J. Mangan
- , Daniel V. Sietsema
- & Rytis Prekeris
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Article
| Open AccessThe transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis
GRIP1 cooperates with the glucocorticoid receptor to repress inflammatory genes. Here the authors show that GRIP1 also controls macrophage polarization, by promoting KLF4-driven activation in response to IL-4, and that mice lacking GRIP1 in macrophages develop severe metabolic dysfunction on a high-fat diet.
- Maddalena Coppo
- , Yurii Chinenov
- & Inez Rogatsky
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Article
| Open AccessNon-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
In mature neurons the centrosome no longer functions as the main microtubule organizer and it is unclear how ordered microtubule arrays are assembled. Here, the authors show that in post-mitotic neurons this process depends on non-centrosomal nucleation mediated by the protein complex augmin and the nucleator gamma-TuRC.
- Carlos Sánchez-Huertas
- , Francisco Freixo
- & Jens Lüders
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Article
| Open AccessAlix-mediated assembly of the actomyosin–tight junction polarity complex preserves epithelial polarity and epithelial barrier
Correct assembly of intercellular junctions is required to maintain epithelial polarity and barrier function. Here Campos et al. show that the scaffold protein Alix interacts with F-actin, the Par complex and ZO-1 to ensure the formation and maintenance of the actomyosin tight junction complex in choroid plexus epithelium.
- Yvan Campos
- , Xiaohui Qiu
- & Alessandra d’Azzo
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Article
| Open AccessaPKC regulates apical localization of Lgl to restrict elongation of microridges in developing zebrafish epidermis
Squamous epithelia present actin-rich microridges on the apical surface, but the mechanism of their formation is not known. Here the authors show that, in zebrafish epidermis, the exclusion of the basolateral regulator Lgl from the apical domain by atypical protein kinase C prevents precocious elongation and fusion of microridges.
- Renuka Raman
- , Indraneel Damle
- & Mahendra Sonawane
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Article
| Open AccessA lateral signalling pathway coordinates shape volatility during cell migration
Migrating cells display dynamic morphologies that are coordinated by signalling pathways. Here the authors identify a lateral signalling pathway, comprised of the planar cell polarity protein Pk1 and Arhgap21/23, that regulates fluctuations in cell shape during productive cell migration.
- Liang Zhang
- , Valbona Luga
- & Jeffrey L. Wrana
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Article
| Open AccessDchs1–Fat4 regulation of polarized cell behaviours during skeletal morphogenesis
How the shape of the sternum is regulated is unclear. Here, the authors identify the Dchs1-Fat4-planar cell polarity pathway as controlling cell orientation and cell intercalation of mesenchymal cells that form skeletal condensations for the mouse sternum, which defines the relative dimensions of the sternum.
- Yaopan Mao
- , Anna Kuta
- & Philippa Francis-West
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Article
| Open AccessRepulsive cues combined with physical barriers and cell–cell adhesion determine progenitor cell positioning during organogenesis
The precise positioning of organ progenitor cells is essential for organ development and function. Here the authors use live imaging and mathematical modelling to show that the confinement of a motile progenitor cell population results from coupled physical barriers and cell-cell interactions.
- Azadeh Paksa
- , Jan Bandemer
- & Erez Raz
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Article
| Open AccessRab35 GTPase couples cell division with initiation of epithelial apico-basal polarity and lumen opening
Establishment and maintenance of apico-basal polarity in epithelial organs needs to be tightly coupled with cell division. Here the authors show that the Rab35 GTPase tethers intracellular vesicles containing key apical determinants at the cleavage site, connecting cytokinesis to apico-basal polarity.
- Kerstin Klinkert
- , Murielle Rocancourt
- & Arnaud Echard
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Article
| Open AccessPositioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling
Planar cell polarity (PCP) contributes to cellular orientation during development but how this is regulated in Drosophilais unclear. Here, the authors identify Frizzled-PCP signalling as regulating polarised centriole positioning in the wing disc.
- Jose Maria Carvajal-Gonzalez
- , Angel-Carlos Roman
- & Marek Mlodzik
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Article
| Open AccessActin nucleation at the centrosome controls lymphocyte polarity
Cell polarity is marked by re-orientation of the centrosome, but the mechanisms governing centrosome polarization are poorly understood. Here Obino et al. show that in lymphocytes centrosome-associated Arp2/3 nucleates actin that tethers the centrosome to the nucleus; activation depletes Arp2/3 from the centrosome and frees it from the nucleus.
- Dorian Obino
- , Francesca Farina
- & Ana-Maria Lennon-Duménil
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Article
| Open AccessVinculin controls talin engagement with the actomyosin machinery
The mechanosensitive proteins talin and vinculin mediate the linkage between integrin-bound extracellular matrix and the actin cytoskeleton. Here the authors dissect distinct roles for two actin-binding sites within talin on adhesion complex assembly and maturation, which are regulated by vinculin binding to talin.
- Paul Atherton
- , Ben Stutchbury
- & Christoph Ballestrem
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Article
| Open AccessThe alternative splicing factor Nova2 regulates vascular development and lumen formation
The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro et al. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish.
- Costanza Giampietro
- , Gianluca Deflorian
- & Claudia Ghigna
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Article |
HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity
Retracted neurites and disorganized actin filaments are major components of senile plaques and neurofibrillary tangles—hallmarks of Alzheimer's disease. Here the authors show that soluble ß-amyloid impairs action potential firing by disrupting actin and microtubule filaments through the inhibition of HDAC6 and activation of RhoA.
- Hanako Tsushima
- , Marco Emanuele
- & Evelina Chieregatti
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Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing Snail expression
AF6, an essential protein for the organization of cell-to-cell junctions and development, is aberrantly expressed in several tumors but its role in pancreatic cancer is not clear. Here the authors show that in pancreatic cancer, loss of AF6 expression leads to induction of the EMT transcription factor Snail.
- Yi Xu
- , Renxu Chang
- & Lixing Zhan
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Article |
The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo
Planar cell polarity (PCP) is generated by the restricted localization of membrane-bound multiprotein complexes, but how they are trafficked to the correct location is unknown. Here, the authors show that the GTPase ARF1 and the AP-1 adaptor complex are major regulators of PCP protein trafficking in vivo.
- Jose Maria Carvajal-Gonzalez
- , Sophie Balmer
- & Marek Mlodzik
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Article
| Open AccessMyeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization
In response to microbial ligands, IRF5 promotes pro-inflammatory M1 macrophage activation and production of nitrous oxide. Here the authors show that nitrous oxide modifies IRF5 tyrosine residues as a negative feedback, limiting the inflammatory response and protecting from endotoxin shock.
- Geming Lu
- , Ruihua Zhang
- & Huabao Xiong
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Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis
The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis but the extracellular cues regulating this process are largely unknown. Here, the authors show that Semaphorin3B released from the floor plate and the nascent choroid plexus controls progenitor division orientation in the developing mouse spinal cord.
- Elise Arbeille
- , Florie Reynaud
- & Valérie Castellani
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Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization
Kidney epithelial cells grown in 3D culture form polarized cysts in which basal membranes surround a lumen. Peng et al.show that the p110δ subunit of phosphoinositide 3-kinase contributes to the formation of these structures by influencing focal adhesion at the basal membrane.
- Juan Peng
- , Aline Awad
- & Ama Gassama-Diagne
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Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent
Specific Schwann cell-axon interactions control the initiation of myelination in the peripheral nervous system. Here the authors show that the tumour suppressor protein Lkb1 is asymmetrically localized to the Schwann cell-axon interface and co-localizes with the polarity protein Par-3 to establish the initiation of myelination.
- Yun-An A. Shen
- , Yan Chen
- & Q. Richard Lu
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Spatial control of Cdc42 signalling by a GM130–RasGRF complex regulates polarity and tumorigenesis
The small GTPase Cdc42 is an important regulator of cell polarity that localizes to both the plasma membrane and to the Golgi. Baschieri et al.show that the Golgi pool of Cdc42 is regulated by GM130–RasGRF, and that deregulation of this pathway is associated with loss of polarity and tumorigenesis.
- Francesco Baschieri
- , Stefano Confalonieri
- & Hesso Farhan
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The ubiquitin ligase PDZRN3 is required for vascular morphogenesis through Wnt/planar cell polarity signalling
Wnt/planar cell polarity (PCP) signalling regulates angiogenesis in vertebrates. Here the authors show that the E3 ubiquitin ligase PDZRN3 ubiquitinates the PCP-signalling protein Dishevelled 3 to promote Wnt/PCP signalling, directing embryonic and postnatal remodelling of the vasculature in mouse.
- Raj N. Sewduth
- , Béatrice Jaspard-Vinassa
- & Cécile Duplàa