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https://www.readbyqxmd.com/read/29464029/the-protein-kinase-sik-downregulates-the-polarity-protein-par3
#1
Michael Vanlandewijck, Mahsa Shahidi Dadras, Marta Lomnytska, Tanzila Mahzabin, Martin Lee Miller, Christer Busch, Søren Brunak, Carl-Henrik Heldin, Aristidis Moustakas
The multifunctional cytokine transforming growth factor β (TGFβ) controls homeostasis and disease during embryonic and adult life. TGFβ alters epithelial cell differentiation by inducing epithelial-mesenchymal transition (EMT), which involves downregulation of several cell-cell junctional constituents. Little is understood about the mechanism of tight junction disassembly by TGFβ. We found that one of the newly identified gene targets of TGFβ, encoding the serine/threonine kinase salt-inducible kinase 1 (SIK), controls tight junction dynamics...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29444419/pak1-kinase-maintains-apical-membrane-identity-in-epithelia
#2
Mario Aguilar-Aragon, Ahmed Elbediwy, Valentina Foglizzo, Georgina C Fletcher, Vivian S W Li, Barry J Thompson
Epithelial cells are polarized along their apical-basal axis by the action of the small GTPase Cdc42, which is known to activate the aPKC kinase at the apical domain. However, loss of aPKC kinase activity was reported to have only mild effects on epithelial cell polarity. Here, we show that Cdc42 also activates a second kinase, Pak1, to specify apical domain identity in Drosophila and mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1 kinase leads to a complete loss of epithelial polarity and morphology, with cells losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29440511/structural-basis-for-the-interaction-between-the-cell-polarity-proteins-par3-and-par6
#3
Fabian A Renschler, Susanne R Bruekner, Paulin L Salomon, Amrita Mukherjee, Lars Kullmann, Mira C Schütz-Stoffregen, Christine Henzler, Tony Pawson, Michael P Krahn, Silke Wiesner
Polarity is a fundamental property of most cell types. The Par protein complex is a major driving force in generating asymmetrically localized protein networks and consists of atypical protein kinase C (aPKC), Par3, and Par6. Dysfunction of this complex causes developmental abnormalities and diseases such as cancer. We identified a PDZ domain-binding motif in Par6 that was essential for its interaction with Par3 in vitro and for Par3-mediated membrane localization of Par6 in cultured cells. In fly embryos, we observed that the PDZ domain-binding motif was functionally redundant with the PDZ domain in targeting Par6 to the cortex of epithelial cells...
February 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29399897/%C3%AE-tocopherol-promotes-hacat-keratinocyte-wound-repair-through-the-regulation-of-polarity-proteins-leading-to-the-polarized-cell-migration
#4
Yosuke Horikoshi, Kouki Kamizaki, Takehiko Hanaki, Masaki Morimoto, Yoshinori Kitagawa, Kazuhiro Nakaso, Chiaki Kusumoto, Tatsuya Matsura
In many developed countries including Japan, how to care the bedridden elderly people with chronic wounds such as decubitus becomes one of the most concerned issues. Although antioxidant micronutrients including vitamin E, especially α-tocopherol (α-Toc), are reported to shorten a period of wound closure, the promoting effect of α-Toc on wound healing independent of its antioxidant activity remains to be fully elucidated. The aim of this study was to examine whether α-Toc affects wound-mediated HaCaT keratinocyte polarization process including the recruitment of polarity regulating proteins, leading to wound repair independently of its antioxidant activity...
February 5, 2018: BioFactors
https://www.readbyqxmd.com/read/29361565/rap1-acts-via-multiple-mechanisms-to-position-canoe-afadin-and-adherens-junctions-and-mediate-apical-basal-polarity-establishment
#5
Teresa T Bonello, Kia Z Perez-Vale, Kaelyn D Sumigray, Mark Peifer
Epithelial apical-basal polarity drives assembly and function of most animal tissues. Polarity initiation requires cell-cell adherens junction assembly at the apical-basolateral boundary. The mechanisms underlying polarity establishment remain key issues. Drosophila embryos provide a superb model, as 6000 polarized cells assemble simultaneously. Current data place the actin-junctional linker Canoe (Afadin's fly homolog) at the top of the polarity hierarchy, where it directs Bazooka/Par3 and adherens junctions positioning...
December 22, 2017: Development
https://www.readbyqxmd.com/read/29356040/basolateral-cd147-induces-hepatocyte-polarity-loss-by-e-cadherin-ubiquitination-and-degradation-in-hepatocellular-carcinoma-progress
#6
Meng Lu, Jiao Wu, Zhi-Wei Hao, Yu-Kui Shang, Jing Xu, Gang Nan, Xia Li, Zhi-Nan Chen, Huijie Bian
Hepatocytes are epithelial cells with highly specialized polarity. The disorder and loss of hepatocyte polarity lead to the weakness of cell adhesion and connection, the induction of epithelial-mesenchymal transition and eventually the occurrence of hepatocellular carcinoma (HCC). CD147, a tumor-related glycoprotein, promotes epithelial-mesenchymal transition and the invasion of HCC. However, the function of CD147 in hepatocyte depolarization is unknown. Here we identified that CD147 was basolaterally polarized in hepatocyte membrane of liver tissues and HepG2 cells...
January 21, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220829/decreased-expression-of-the-polarity-regulatory-par-complex-predicts-poor-prognosis-of-the-patients-with-colorectal-adenocarcinoma
#7
Min-Kyung Yeo, Jin-Man Kim, Kwang-Sun Suh, Seok-Hyung Kim, Ok-Jun Lee, Kyung-Hee Kim
Partitioning defective (Par) proteins regulate cell polarity and differentiation. Par3, Par6β, and protein kinase Cζ (PKCζ), which are PAR complex members, have been shown to be associated with oncogenesis and progression. Herein, we report the expression pattern and clinical relevance of Par3, Par6β, and PKCζ in colorectal adenocarcinoma (CRAC). A total of 393 primary CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia, and 41 nontumor colorectal tissue samples were examined by immunohistochemistry and Western blot assays for Par3, Par6β, and PKCζ protein expressions...
December 5, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29206870/loss-of-polarity-alters-proliferation-and-differentiation-in-low-grade-endometrial-cancers-by-disrupting-notch-signaling
#8
Erin Williams, Alejandro Villar-Prados, Jessica Bowser, Russell Broaddus, Andrew B Gladden
Cell adhesion and apicobasal polarity together maintain epithelial tissue organization and homeostasis. Loss of adhesion has been described as a prerequisite for the epithelial to mesenchymal transition. However, what role misregulation of apicobasal polarity promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization of the apical polarity protein Par3 and Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by decreased Notch signaling, and altered Notch receptor localization...
2017: PloS One
https://www.readbyqxmd.com/read/29065046/cell-polarity-and-par-complex-likely-to-be-involved-in-dexamethasone-induced-cleft-palate
#9
Li Ma, Bing Shi, Qian Zheng
Accumulating studies demonstrated that PAR complex contributed to the establishment and maintenance of cell polarity which was fundamental to many aspects of cell and developmental biology. The purpose of this study was to investigate whether dexamethasone (DEX) could downregulate the PAR complex and disrupt cell polarity in palatal epithelium during palatal fusion in mice. The C57BL/6J mice were selected for the experiment. Pregnant mice in control group and DEX-treated group were injected intraperitoneally with 0...
October 23, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29056580/role-of-the-crumbs-proteins-in-ciliogenesis-cell-migration-and-actin-organization
#10
REVIEW
Elsa Bazellières, Veronika Aksenova, Magali Barthélémy-Requin, Dominique Massey-Harroche, André Le Bivic
Epithelial cell organization relies on a set of proteins that interact in an intricate way and which are called polarity complexes. These complexes are involved in the determination of the apico-basal axis and in the positioning and stability of the cell-cell junctions called adherens junctions at the apico-lateral border in invertebrates. Among the polarity complexes, two are present at the apical side of epithelial cells. These are the Par complex including aPKC, PAR3 and PAR6 and the Crumbs complex including, CRUMBS, PALS1 and PATJ/MUPP1...
October 19, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29017577/elevated-expression-of-par3-promotes-prostate-cancer-metastasis-by-forming-a-par3-apkc-kibra-complex-and-inactivating-the-hippo-pathway
#11
Pei-Jie Zhou, Wei Xue, Jinliang Peng, Yanqing Wang, Lianzi Wei, Ziqiang Yang, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
BACKGROUND: Prostate cancer (PCa) is one of the most frequent tumors and leading cause of cancer deaths among males worldwide. The majority of deaths are due to recurrence and subsequent development of the metastatic cancer. Although loss or dislocalization of polarity proteins has been implicated in embryogenesis deficiency and tumorigenesis, association of polarity protein expression levels with tumor metastasis remains unclear. METHODS: Bioinformatics, qRT-PCR, western blot and immunohistochemical (IHC) analyses were used to examine expression of Par3, a key component of polarity-associated partitioning defective (PAR) complex, in primary and metastatic clinical PCa samples...
October 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28825699/an-apical-mrck-driven-morphogenetic-pathway-controls-epithelial-polarity
#12
Ceniz Zihni, Evi Vlassaks, Stephen Terry, Jeremy Carlton, Thomas King Chor Leung, Michael Olson, Franck Pichaud, Maria Susana Balda, Karl Matter
Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning-defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown...
September 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28790366/amotl2-integrates-polarity-and-junctional-cues-to-modulate-cell-shape
#13
Sara Hultin, Aravindh Subramani, Sebastian Hildebrand, Yujuan Zheng, Arindam Majumdar, Lars Holmgren
The assembly of individual epithelial or endothelial cells into a tight cellular sheet requires stringent control of cell packing and organization. These processes are dependent on the establishment and further integration of cellular junctions, the cytoskeleton and the formation of apical-basal polarity. However, little is known how these subcellular events are coordinated. The (Angiomotin) Amot protein family consists of scaffold proteins that interact with junctional cadherins, polarity proteins and the cytoskeleton...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28665270/meru-couples-planar-cell-polarity-with-apical-basal-polarity-during-asymmetric-cell-division
#14
Jennifer J Banerjee, Birgit L Aerne, Maxine V Holder, Simon Hauri, Matthias Gstaiger, Nicolas Tapon
Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation...
June 30, 2017: ELife
https://www.readbyqxmd.com/read/28545845/claudins-are-essential-for-cell-shape-changes-and-convergent-extension-movements-during-neural-tube-closure
#15
Amanda I Baumholtz, Annie Simard, Evanthia Nikolopoulou, Marcus Oosenbrug, Michelle M Collins, Anna Piontek, Gerd Krause, Jörg Piontek, Nicholas D E Greene, Aimee K Ryan
During neural tube closure, regulated changes at the level of individual cells are translated into large-scale morphogenetic movements to facilitate conversion of the flat neural plate into a closed tube. Throughout this process, the integrity of the neural epithelium is maintained via cell interactions through intercellular junctions, including apical tight junctions. Members of the claudin family of tight junction proteins regulate paracellular permeability, apical-basal cell polarity and link the tight junction to the actin cytoskeleton...
August 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28400336/aspp2-suppresses-invasion-and-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-by-inhibiting-smad7-degradation-mediated-by-e3-ubiquitin-ligase-itch-in-gastric-cancer
#16
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...
July 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28358000/the-par3-polarity-protein-is-an-exocyst-receptor-essential-for-mammary-cell-survival
#17
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
https://www.readbyqxmd.com/read/28319357/par3-in-chick-lens-placode-development
#18
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...
June 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28143902/pdzrn3-destabilizes-endothelial-cell-cell-junctions-through-a-pkc%C3%AE-containing-polarity-complex-to-increase-vascular-permeability
#19
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
https://www.readbyqxmd.com/read/28096290/the-epidermal-polarity-protein-par3-is-a-non-cell-autonomous-suppressor-of-malignant-melanoma
#20
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
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