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Apical ezrin

J Vaquero, T H Nguyen Ho-Bouldoires, A Clapéron, L Fouassier
The transmission of cellular information requires fine and subtle regulation of proteins that need to interact in a coordinated and specific way to form efficient signaling networks. The spatial and temporal coordination relies on scaffold proteins. Thanks to protein interaction domains such as PDZ domains, scaffold proteins organize multiprotein complexes enabling the proper transmission of cellular information through intracellular networks. NHERF1/EBP50 is a PDZ-scaffold protein that was initially identified as an organizer and regulator of transporters and channels at the apical side of epithelia through actin-binding ezrin-moesin-radixin proteins...
January 9, 2017: Oncogene
Kedsarin Fong-Ngern, Arada Vinaiphat, Visith Thongboonkerd
Pathogenic mechanisms of kidney stone disease remained unclear. This study investigated its initial cellular/molecular mechanisms when calcium oxalate monohydrate (COM) crystal adhered to renal tubular cells. Transmission electron microscopy revealed decreased length and density of microvilli, whereas Western blot analysis showed that whole-cell ezrin (a microvillus-stabilizing protein), not β-actin, was decreased in COM-treated cells. Immunofluorescence staining, followed by laser-scanning confocal microscopy and subcellular fractionations, revealed decreases in both ezrin and F-/β-actin at apical membrane...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Brenda Demacopulo, Baltazar Eduardo Lema, Rómulo Luis Cabrini, Erica Lorena Kreimann
NHERF1 is an adaptor protein expressed in the apical membrane of polarized epithelia, which interacts with the EZRIN-Radixin-Moesin (ERM) family of proteins connecting signaling pathways to the cell cytoskeleton. NHERF1 and EZRIN cooperate in the maintenance of the apical microvilli in polarized epithelial cells. In several types of cancers, NHERF1 and EZRIN are displaced from the apical compartment to the cytoplasm and nuclei of cancer cells. At the present, the distribution of NHERF1 in ovarian tumors is not well known...
October 2016: Acta Histochemica
Yvonne Schaletzki, Marie-Luise Kromrey, Susanne Bröderdorf, Elke Hammer, Markus Grube, Paul Hagen, Sonja Sucic, Michael Freissmuth, Uwe Völker, Andreas Greinacher, Bernhard H Rauch, Heyo K Kroemer, Gabriele Jedlitschky
The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter...
October 20, 2016: Thrombosis and Haemostasis
Gabriel Luna, Geoffrey P Lewis, Kenneth A Linberg, Bo Chang, Quiri Hu, Peter J Munson, Arvydas Maminishkis, Sheldon S Miller, Steven K Fisher
PURPOSE: The purpose of this study was to examine the rpea1 mouse whose retina spontaneously detaches from the underlying RPE as a potential model for studying the cellular effects of serous retinal detachment (SRD). METHODS: Optical coherence tomography (OCT) was performed immediately prior to euthanasia; retinal tissue was subsequently prepared for Western blotting, microarray analysis, immunocytochemistry, and light and electron microscopy (LM, EM). RESULTS: By postnatal day (P) 30, OCT, LM, and EM revealed the presence of small shallow detachments that increased in number and size over time...
September 1, 2016: Investigative Ophthalmology & Visual Science
Sabine Kluge, Yvonne Genzel, Kim Laus, Anja Serve, Antje Pflugmacher, Britta Peschel, Erdmann Rapp, Udo Reichl
With the aim to adapt high-yield adherent cell lines to suspension growth, Madin Darby canine kidney (MDCK) suspension cells were developed recently that achieved comparable influenza virus yields despite an early induction of apoptosis compared to the parental adherent cell line. For both cell lines, a comprehensive study under comparable infection conditions is performed comprising information on: time course of viral infection, antiviral state of cells, virus-induced apoptosis, and virus-induced cellular protein expression for early and late infection with influenza A/PuertoRico/8/34 H1N1...
October 2016: Biotechnology Journal
Zhufeng Yang, Susan E Zimmerman, Jun Tsunezumi, Caitlin Braitsch, Cary Trent, David M Bryant, Ondine Cleaver, Consuelo González-Manchón, Denise K Marciano
Previous studies have shown CD34 family member Podocalyxin is required for epithelial lumen formation in vitro. We demonstrate that Endoglycan, a CD34 family member with homology to Podocalyxin, is produced prior to lumen formation in developing nephrons. Endoglycan localizes to Rab11-containing vesicles in nephron progenitors, and then relocalizes to the apical surface as progenitors epithelialize. Once an apical/luminal surface is formed, Endoglycan (and the actin-binding protein Ezrin) localize to large, intraluminal structures that may be vesicles/exosomes...
October 1, 2016: Developmental Biology
Wenyan Xu, Miaomiao Jin, Ruikun Hu, Hong Wang, Fan Zhang, Shiaulou Yuan, Ying Cao
Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear...
January 2017: Journal of the American Society of Nephrology: JASN
In Kyoung Mah, Rachel Soloff, Audrey K Izuhara, Daniel L Lakeland, Charles Wang, Francesca V Mariani
Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation...
August 1, 2016: Developmental Biology
Maria-Magdalena Georgescu, Bret C Mobley, Brent A Orr, Ping Shang, Norman L Lehman, Xiaoping Zhu, Thomas J O'Neill, Veena Rajaram, Kimmo J Hatanpaa, Charles F Timmons, Jack M Raisanen
The adaptor protein NHERF1 (Na/H exchanger-3 regulatory factor-1) and its associated ezrin-radixin-moesin-merlin/neurofibromin-2 (ERM-NF2) family proteins are required for epithelial morphogenesis and have been implicated in cancer progression. NHERF1 is expressed in ependymal cells and constitutes a highly sensitive diagnostic marker for ependymoma, where it labels membrane polarity structures. Since NHERF1 and ERM-NF2 proteins show polarized expression in choroid plexus (CP) cells, we tested their diagnostic utility in CP neoplasms...
May 27, 2016: Acta Neuropathologica Communications
Katharina Natalia Richter, Daniel Rolke, Wolfgang Blenau, Otto Baumann
The honeybee hypopharyngeal gland consists in numerous units, each comprising a secretory cell and a canal cell. The secretory cell discharges its products into a convoluted tubular membrane system, the canaliculus, which is surrounded at regular intervals by rings of actin filaments. Using probes for various membrane components, we analyze the organization of the secretory cells relative to the apicobasal configuration of epithelial cells. The canaliculus was defined by labeling with an antibody against phosphorylated ezrin/radixin/moesin (pERM), a marker protein for the apical membrane domain of epithelial cells...
October 2016: Cell and Tissue Research
Andrew M Tilston-Lünel, Kathryn E Haley, Nicolas F Schlecht, Yanhua Wang, Abigail L D Chatterton, Susana Moleirinho, Ailsa Watson, Harinder S Hundal, Michael B Prystowsky, Frank J Gunn-Moore, Paul A Reynolds
Crumbs 3 (CRB3) is a component of epithelial junctions that has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions (TJs). However, significantly we demonstrate that the 4.1-ezrin-radixin-moesin (FERM)-binding motif (FBM) of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b...
April 18, 2016: Journal of Molecular Cell Biology
Anna C Abbattiscianni, Maria Favia, Maria T Mancini, Rosa A Cardone, Lorenzo Guerra, Stefania Monterisi, Stefano Castellani, Onofrio Laselva, Francesca Di Sole, Massimo Conese, Manuela Zaccolo, Valeria Casavola
The most common mutation of the cystic fibrosis transmembrane regulator (CFTR) gene, F508del, produces a misfolded protein resulting in its defective trafficking to the cell surface and an impaired chloride secretion. Pharmacological treatments partially rescue F508del CFTR activity either directly by interacting with the mutant protein and/or indirectly by altering the cellular protein homeostasis. Here, we show that the phosphorylation of ezrin together with its binding to phosphatidylinositol-4,5-bisphosphate (PIP2) tethers the F508del CFTR to the actin cytoskeleton, stabilizing it on the apical membrane and rescuing the sub-membrane compartmentalization of cAMP and activated PKA...
March 15, 2016: Journal of Cell Science
Kenichiro Taniguchi, Yue Shao, Ryan F Townshend, Yu-Hwai Tsai, Cynthia J DeLong, Shawn A Lopez, Srimonta Gayen, Andrew M Freddo, Deming J Chue, Dennis J Thomas, Jason R Spence, Benjamin Margolis, Sundeep Kalantry, Jianping Fu, K Sue O'Shea, Deborah L Gumucio
We demonstrate that dissociated human pluripotent stem cells (PSCs) are intrinsically programmed to form lumens. PSCs form two-cell cysts with a shared apical domain within 20 hr of plating; these cysts collapse to form monolayers after 5 days. Expression of pluripotency markers is maintained throughout this time. In two-cell cysts, an apical domain, marked by EZRIN and atypical PKCζ, is surrounded by apically targeted organelles (early endosomes and Golgi). Molecularly, actin polymerization, regulated by ARP2/3 and mammalian diaphanous-related formin 1 (MDIA), promotes lumen formation, whereas actin contraction, mediated by MYOSIN-II, inhibits this process...
December 8, 2015: Stem Cell Reports
Cécile Sauvanet, Jessica Wayt, Thaher Pelaseyed, Anthony Bretscher
Microvilli are actin-based structures found on the apical aspect of many epithelial cells. In this review, we discuss different types of microvilli, as well as comparisons with actin-based sensory stereocilia and filopodia. Much is known about the actin-bundling proteins of these structures; we summarize recent studies that focus on the components of the microvillar membrane. We pay special attention to mechanisms of membrane microfilament attachment by the ezrin/radixin/moesin family and regulation of this protein family...
2015: Annual Review of Cell and Developmental Biology
Grégoire Michaux, Dominique Massey-Harroche, Ophélie Nicolle, Marion Rabant, Nicole Brousse, Olivier Goulet, André Le Bivic, Frank M Ruemmele
BACKGROUND INFORMATION: Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients...
January 2016: Biology of the Cell
Murni H Jais, Reena R Md Zin, Nur A Muhd Hanapi, Siti A Md Ali
Ezrin, a membrane-linking protein, has been shown to play an important role in the carcinogenesis of infiltrating breast ductal carcinoma and its strong expression has been used to predict poor prognosis in patients with breast carcinoma. In this study, we compared ezrin protein distribution pattern in benign breast disease and breast cancer molecular subtypes and evaluated their association with clinicopathologic variables. A total of 376 breast cases (142 benign and 234 malignant cases) were studied. Immunohistochemical analysis for ezrin was performed and its expression was observed in terms of its distribution, intensity, and proportion of cells reactive for ezrin...
January 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
Yoshikazu Hirate, Shino Hirahara, Ken-Ichi Inoue, Hiroshi Kiyonari, Hiroshi Niwa, Hiroshi Sasaki
In preimplantation mouse embryos, the Hippo signaling pathway plays a central role in regulating the fates of the trophectoderm (TE) and the inner cell mass (ICM). In early blastocysts with more than 32 cells, the Par-aPKC system controls polarization of the outer cells along the apicobasal axis, and cell polarity suppresses Hippo signaling. Inactivation of Hippo signaling promotes nuclear accumulation of a coactivator protein, Yap, leading to induction of TE-specific genes. However, whether similar mechanisms operate at earlier stages is not known...
October 2015: Development, Growth & Differentiation
Audra M A Shadforth, Shuko Suzuki, Christina Theodoropoulos, Neil A Richardson, Traian V Chirila, Damien G Harkin
Silk fibroin provides a promising biomaterial for ocular tissue reconstruction, including the damaged outer blood-retinal barrier of patients afflicted with age-related macular degeneration (AMD). The aim of the present study was to evaluate the function of retinal pigment epithelial (RPE) cells in vitro, when grown on fibroin membranes manufactured to a thickness similar to that of Bruch's membrane (3 µm). Confluent cultures of RPE cells (ARPE-19) were established on fibroin membranes and maintained under conditions designed to promote maturation over 4 months...
October 9, 2015: Journal of Tissue Engineering and Regenerative Medicine
Hao Jiang, Wenwen Wang, Yin Zhang, William W Yao, Jiying Jiang, Bo Qin, Wendy Y Yao, Fusheng Liu, Huihui Wu, Tarsha L Ward, Chun Wei Chen, Lifang Liu, Xia Ding, Xing Liu, Xuebiao Yao
The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion...
November 20, 2015: Journal of Biological Chemistry
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