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par3 polarity

Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Naoto Iwai, Kei Terasaki, Osamu Dohi, Hikaru Hashimoto, Hayato Fukui, Yutaka Inada, Akifumi Fukui, Masayasu Jo, Michihisa Moriguchi, Taichiro Nishikawa, Atushi Umemura, Kanji Yamaguchi, Hiroyuki Konishi, Yuji Naito, Yoshito Itoh
ASPP2 regulates cell polarity and cell-cell adhesion by binding to, and co-localizing with PAR3 at tight junctions. Here we show a novel role of ASPP2 in suppressing gastric cancer (GC) invasiveness. Immunoprecipitation and immunofluorescence analyses showed that ASPP2 promoted the recruitment of PAR3 to cell-cell junctions in GC cells. Diminished expression of ASPP2 and loss of junctional PAR3 localization were significantly associated with diffuse-type histology, deeper invasion depth, positive peritoneal dissemination and worse prognosis in primary GC...
April 9, 2017: Cancer Letters
Syed Mukhtar Ahmed, Ian G Macara
The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 polarity protein associates with TJs but has no known function in membrane traffic. We now show that, unexpectedly, Par3 is essential for mammary cell survival. Par3 silencing causes apoptosis, triggered by phosphoinositide trisphosphate depletion and decreased Akt phosphorylation, resulting from failure of the exocyst to deliver basolateral proteins to the cortex...
March 30, 2017: Nature Communications
Maraysa de Oliveira Melo, Ricardo Moraes Borges, Chao Yun Irene Yan
The lens originates from a simple cuboidal epithelium, which, on its basal side, contacts the optic vesicle, whilst facing the extraembryonic environment on its apical side. As this epithelium changes into the pseudostratified lens placode, its cells elongate and become narrower at their apical ends. This is due to the formation of an apical actin network, whose appearance is restricted to cells of the placodal region, as a result of region-specific signaling mechanisms that remain largely unknown. Here, we investigated the role of the polarity protein PAR3 and the phosphorylation state of its Threonine 833 (T833) aPKC-binding site in the recruitment of aPKC and in the establishment of actin network in the chick lens placode...
March 20, 2017: Genesis: the Journal of Genetics and Development
Raj N Sewduth, Héléna Kovacic, Béatrice Jaspard-Vinassa, Vincent Jecko, Thomas Wavasseur, Nicolas Fritsch, Mathieu Pernot, Sylvie Jeaningros, Etienne Roux, Pascale Dufourcq, Thierry Couffinhal, Cécile Duplàa
Endothelial cells serve as a barrier between blood and tissues. Maintenance of the endothelial cell barrier depends on the integrity of intercellular junctions, which is regulated by a polarity complex that includes the ζ isoform of atypical protein kinase C (PKCζ) and partitioning defective 3 (PAR3). We revealed that the E3 ubiquitin ligase PDZ domain-containing ring finger 3 (PDZRN3) regulated endothelial intercellular junction integrity. Endothelial cell-specific overexpression of Pdzrn3 led to early embryonic lethality with severe hemorrhaging and altered organization of endothelial intercellular junctions...
January 31, 2017: Science Signaling
Melina Mescher, Peter Jeong, Sina K Knapp, Matthias Rübsam, Michael Saynisch, Marina Kranen, Jennifer Landsberg, Max Schlaak, Cornelia Mauch, Thomas Tüting, Carien M Niessen, Sandra Iden
Melanoma, an aggressive skin malignancy with increasing lifetime risk, originates from melanocytes (MCs) that are in close contact with surrounding epidermal keratinocytes (KCs). How the epidermal microenvironment controls melanomagenesis remains poorly understood. In this study, we identify an unexpected non-cell autonomous role of epidermal polarity proteins, molecular determinants of cytoarchitecture, in malignant melanoma. Epidermal Par3 inactivation in mice promotes MC dedifferentiation, motility, and hyperplasia and, in an autochthonous melanoma model, results in increased tumor formation and lung metastasis...
February 2017: Journal of Experimental Medicine
Christina B Wölwer, Nathan Gödde, Luke B Pase, Imogen A Elsum, Krystle Y B Lim, Faruk Sacirbegovic, Carl R Walkley, Sarah Ellis, Shigeo Ohno, Fumio Matsuzaki, Sarah M Russell, Patrick O Humbert
Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Here we investigated gene expression of members of the Par, Scribble and Pins/Gpsm2 asymmetric cell division complexes in erythroid cells, and functionally tested their role in erythroid enucleation in vivo and ex vivo...
2017: PloS One
Mo Weng, Eric Wieschaus
The polarity protein Par3/Bazooka (Baz) has been established as a central component of the apical basal polarity system that determines the position of cell-cell junctions in epithelial cells. Consistent with that view, we show that shortly before gastrulation in Drosophila, Baz protein in the mesoderm is down-regulated from junctional sites in response to Snail (Sna) expression. This down-regulation leads to a specific decrease in adherens junctions without affecting other E-Cadherin pools. However, we further show that, interactions between Baz and junctions are not unidirectional...
February 15, 2017: Developmental Biology
Gianluca Baldanzi, Valentina Bettio, Valeria Malacarne, Andrea Graziani
Diacylglycerol kinases (DGKs) terminate diacylglycerol (DAG) signaling and promote phosphatidic acid (PA) production. Isoform specific regulation of DGKs activity and localization allows DGKs to shape the DAG and PA gradients. The capacity of DGKs to constrain the areas of DAG signaling is exemplified by their role in defining the contact interface between T cells and antigen presenting cells: the immune synapse. Upon T cell receptor engagement, both DGK α and ζ metabolize DAG at the immune synapse thus constraining DAG signaling...
2016: Frontiers in Cell and Developmental Biology
Travis R Ruch, David M Bryant, Keith E Mostov, Joanne N Engel
Pathogens can alter epithelial polarity by recruiting polarity proteins to the apical membrane, but how a change in protein localization is linked to polarity disruption is not clear. In this study, we used chemically induced dimerization to rapidly relocalize proteins from the cytosol to the apical surface. We demonstrate that forced apical localization of Par3, which is normally restricted to tight junctions, is sufficient to alter apical membrane identity through its interactions with phosphatidylinositol 3-kinase (PI3K) and the Rac1 guanine nucleotide exchange factor Tiam1...
January 15, 2017: Molecular Biology of the Cell
Hiroe Nakamura, Kazunori Nagasaka, Kei Kawana, Ayumi Taguchi, Yuriko Uehara, Mitsuyo Yoshida, Masakazu Sato, Haruka Nishida, Asaha Fujimoto, Tomoko Inoue, Katsuyuki Adachi, Takeshi Nagamatsu, Takahide Arimoto, Katsutoshi Oda, Yutaka Osuga, Tomoyuki Fujii
BACKGROUND: Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer. METHODS: First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients...
November 17, 2016: BMC Cancer
Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao
The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms...
November 25, 2016: Journal of Biological Chemistry
Emilie Pallesi-Pocachard, Elsa Bazellieres, Annelise Viallat-Lieutaud, Marie-Hélène Delgrossi, Magali Barthelemy-Requin, André Le Bivic, Dominique Massey-Harroche
Polarity protein complexes function during polarized cell migration and a subset of these proteins localizes to the reoriented centrosome during this process. Despite these observations, the mechanisms behind the recruitment of these polarity complexes such as the aPKC/PAR6α complex to the centrosome are not well understood. Here we identify Hook2 as an interactor for the aPKC/PAR6α complex that functions to localize this complex at the centrosome. We first demonstrate that Hook2 is essential for the polarized Golgi re-orientation towards the migration front...
2016: Scientific Reports
Erika V Soriano, Marina E Ivanova, Georgina Fletcher, Philippe Riou, Philip P Knowles, Karin Barnouin, Andrew Purkiss, Brenda Kostelecky, Peter Saiu, Mark Linch, Ahmed Elbediwy, Svend Kjær, Nicola O'Reilly, Ambrosius P Snijders, Peter J Parker, Barry J Thompson, Neil Q McDonald
Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par complex component. It is recruited by Par3/Baz (Bazooka in Drosophila) into epithelial apical domains through high-affinity interaction. Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocalization to adherens junctions (AJs). We show that Par3 conserved region 3 (CR3) forms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access. A CR3 motif flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P-loop/αB/αC contacts...
August 22, 2016: Developmental Cell
Luke Martin McCaffrey, JoAnne Montalbano, Constantina Mihai, Ian G Macara
No abstract text is available yet for this article.
August 8, 2016: Cancer Cell
Benjamin F Brinkmann, Tim Steinbacher, Christian Hartmann, Daniel Kummer, Denise Pajonczyk, Fatemeh Mirzapourshafiyi, Masanori Nakayama, Thomas Weide, Volker Gerke, Klaus Ebnet
Blood vessel tubulogenesis requires the formation of stable cell-to-cell contacts and the establishment of apicobasal polarity of vascular endothelial cells. Cell polarity is regulated by highly conserved cell polarity protein complexes such as the Par3-aPKC-Par6 complex and the CRB3-Pals1-PATJ complex, which are expressed by many different cell types and regulate various aspects of cell polarity. Here we describe a functional interaction of VE-cadherin with the cell polarity protein Pals1. Pals1 directly interacts with VE-cadherin through a membrane-proximal motif in the cytoplasmic domain of VE-cadherin...
September 15, 2016: Molecular Biology of the Cell
Hem C Jha, Zhiguo Sun, Santosh K Upadhyay, Darine W El-Naccache, Rajnish K Singh, Sushil K Sahu, Erle S Robertson
Studies have suggested that Epithelial-Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies...
July 2016: PLoS Pathogens
Peng Zhang, Shuting Wang, Sai Wang, Jing Qiao, Lei Zhang, Zhe Zhang, Zhengjun Chen
Partitioning-defective 3 (Par3), a key component of the evolutionarily conserved polarity PAR complex (Par3/Par6/aPKC), controls cell polarity and contributes to cell migration, proliferation and tumor development. Emerging evidence indicates that cell polarity proteins function as upstream modulators that regulate the Hippo pathway. However, little is known about Par3's involvement in the Hippo pathway. Here, we find Par3 and YAP dynamically co-localize in different subcellular compartments; that is, the membrane, cytoplasm and nucleus, in a cell-density-dependent manner...
2016: Cell Discovery
Noelle J A Ali, Martim Dias Gomes, Ronja Bauer, Susanne Brodesser, Catherin Niemann, Sandra Iden
Partitioning-defective (Par) proteins contribute to multiprotein complexes that drive cell polarity and fate in invertebrates. Of these, the ternary Par3-atypical protein kinase C-Par6 polarity complex mediates asymmetry in various systems, whereas Par3 and aPKC/Par6 can also act independently. aPKC-λ has recently been implicated in epidermal differentiation and stem cell fate; however, whether Par3 contributes to the homeostasis of adult stratified epithelia is currently unknown. Here, we provide functional evidence that epidermal Par3 loss disturbed the inside-out skin barrier, coinciding with altered expression and localization of principle tight junction components, and that epidermal differentiation and thickness were increased...
July 21, 2016: Journal of Investigative Dermatology
Radia Forteza, Yolanda Figueroa, Anastasia Mashukova, Vipin Dulam, Pedro J Salas
The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms ι and ζ), Par6, and Par3 determine asymmetry in several cell types, from Caenorhabditis elegans oocytes to vertebrate epithelia and neurons. We previously showed that aPKC is down-regulated in intestinal epithelia under inflammatory stimulation. Further, expression of constitutively active PKCι decreases NF-κB activity in an epithelial cell line, the opposite of the effect reported in other cells. Here we tested the hypothesis that aPKC has a dual function in epithelia, inhibiting the NF-κB pathway in addition to having a role in apicobasal polarity...
July 15, 2016: Molecular Biology of the Cell
David Jimeno, Eugenio Santos
Despite their homologous structure and central nervous system(CNS) expression patterns, the GRF1 and GRF2 guanine nucleotide exchange factors(GEF) appear to play distinct, non-overlapping functions in cellular excitability, synaptic plasticity or neuromodulation. We recently uncovered a new functional role of GRF2 controlling nuclear migration in cone photoreceptors during postnatal neuroepithelial differentiation of the mouse retina. Analyzing GRF2-KO mice, we detected the specific accumulation of abnormally located, "ectopic" cone photoreceptor nuclei in the photoreceptor segment(PS) layer of their retinas...
January 2, 2017: Small GTPases
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