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Milou Tenhagen, Sjoerd Klarenbeek, Tanya M Braumuller, Ilse Hofmann, Petra van der Groep, Natalie Ter Hoeve, Elsken van der Wall, Jos Jonkers, Patrick W B Derksen
Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120...
July 13, 2016: Journal of Mammary Gland Biology and Neoplasia
Audrey M Hendley, Elayne Provost, Jennifer M Bailey, Yue J Wang, Megan H Cleveland, Danielle Blake, Ross W Bittman, Jeffrey C Roeser, Anirban Maitra, Albert B Reynolds, Steven D Leach
The intracellular protein p120 catenin aids in maintenance of cell-cell adhesion by regulating E-cadherin stability in epithelial cells. In an effort to understand the biology of p120 catenin in pancreas development, we ablated p120 catenin in mouse pancreatic progenitor cells, which resulted in deletion of p120 catenin in all epithelial lineages of the developing mouse pancreas: islet, acinar, centroacinar, and ductal. Loss of p120 catenin resulted in formation of dilated epithelial tubules, expansion of ductal epithelia, loss of acinar cells, and the induction of pancreatic inflammation...
March 1, 2015: Developmental Biology
Werner W Franke, Steffen Rickelt, Ralf Zimbelmann, Yvette Dörflinger, Caecilia Kuhn, Norbert Frey, Hans Heid, Rina Rosin-Arbesfeld
Proteins of the striatin family (striatins 1-4; sizes ranging from 90 to 110 kDa on SDS-polyacrylamide gel electrophoresis) are highly homologous in their amino acid sequences but can differ in their cell-type-specific gene expression patterns and biological functions. In various cell types, we have found one, two or three polypeptides of this evolutionarily old and nearly ubiquitous family of proteins known to serve as scaffold proteins for diverse protein complexes. Light and electron microscopic immunolocalization methods have revealed striatins in mammalian cell-cell adherens junctions (AJs)...
March 2015: Cell and Tissue Research
Nicholas O Markham, Caleb A Doll, Michael R Dohn, Rachel K Miller, Huapeng Yu, Robert J Coffey, Pierre D McCrea, Joshua T Gamse, Albert B Reynolds
p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, whereas p120-1A takes precedence in neurons, fibroblasts, and macrophages. During epithelial-to-mesenchymal transition, E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101-amino acid "head domain" comprising the p120-1A N-terminus...
September 1, 2014: Molecular Biology of the Cell
Lisa M Domke, Steffen Rickelt, Yvette Dörflinger, Caecilia Kuhn, Stefanie Winter-Simanowski, Ralf Zimbelmann, Rina Rosin-Arbesfeld, Hans Heid, Werner W Franke
The seminiferous tubules and the excurrent ducts of the mammalian testis are physiologically separated from the mesenchymal tissues and the blood and lymph system by a special structural barrier to paracellular translocations of molecules and particles: the "blood-testis barrier", formed by junctions connecting Sertoli cells with each other and with spermatogonial cells. In combined biochemical as well as light and electron microscopical studies we systematically determine the molecules located in the adhering junctions of adult mammalian (human, bovine, porcine, murine, i...
September 2014: Cell and Tissue Research
René Keil, Mechthild Hatzfeld
p0071 is an intercellular junction protein of the p120 catenin family. We have identified Rab11a as a novel interaction partner of p0071. p0071 interacted preferentially with active Rab11a. Knockdown experiments revealed an interdependent regulation of both proteins. On the one hand, p0071 depletion induced a perinuclear accumulation of Rab11, suggesting a role of p0071 in the anterograde transport of Rab11 from the pericentrosomal region to the plasma membrane but not in retrograde transport. p0071 as well as Rab11 depletion increased transferrin receptor recycling indicating that p0071-induced Rab11 mislocalization interfered with Rab11 function and shifted recycling from the slow Rab11-dependent pathway to the fast Rab4-dependent pathway...
January 1, 2014: Journal of Cell Science
Alexander Nolze, Jacqueline Schneider, René Keil, Marcell Lederer, Stefan Hüttelmaier, Michael M Kessels, Britta Qualmann, Mechthild Hatzfeld
Loss of fragile X mental retardation protein (FMRP) causes synaptic dysfunction and intellectual disability. FMRP is an RNA-binding protein that controls the translation or turnover of a subset of mRNAs. Identifying these target transcripts is an important step toward understanding the pathology of the disease. Here, we show that FMRP regulates actin organization and neurite outgrowth via the armadillo protein p0071. In mouse embryonic fibroblasts (MEFs) lacking FMRP (Fmr1-), the actin cytoskeleton was markedly reorganized with reduced stress fibers and F-actin/G-actin ratios compared to fibroblasts re-expressing the protein...
November 2013: RNA
Kristine Raaby Jakobsen, Emilie Sørensen, Karin Kathrine Brøndum, Tina Fuglsang Daugaard, Rune Thomsen, Anders Lade Nielsen
BACKGROUND: Protrusions of cancer cells conferrers a vital function for cell migration and metastasis. Protein and RNA localization mechanisms have been extensively examined and shown to play pivotal roles for the functional presence of specific protein components in cancer cell protrusions. METHODS: To describe genome wide RNA localized in protrusions of the metastatic human breast cancer cell line MDA-MB-231 we used Boyden chamber based methodology followed by direct mRNA sequencing...
2013: Journal of Molecular Signaling
René Keil, Jenny Schulz, Mechthild Hatzfeld
P0071 is a member of a subfamily of armadillo proteins that also comprises p120-catenin (p120ctn), δ-catenin/NPRAP, ARVCF and the more distantly related plakophilins 1-3. These proteins share a conserved central domain consisting of a series of repeated motifs, the armadillo repeats, which is flanked by more diverse amino- and carboxy-terminal domains. P0071 and the related proteins were first described as components of adherens junctions with a function in clustering and stabilizing cadherins, thereby controlling intercellular adhesion...
August 2013: Biological Chemistry
Doug A Medvetz, Damir Khabibullin, Venkatesh Hariharan, Pat P Ongusaha, Elena A Goncharova, Tanja Schlechter, Thomas N Darling, Ilse Hofmann, Vera P Krymskaya, James K Liao, Hayden Huang, Elizabeth P Henske
Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. In seeking to elucidate the pathogenesis of BHD, we discovered a physical interaction between folliculin (FLCN), the protein product of the BHD gene, and p0071, an armadillo repeat containing protein that localizes to the cytoplasm and to adherens junctions. Adherens junctions are one of the three cell-cell junctions that are essential to the establishment and maintenance of the cellular architecture of all epithelial tissues...
2012: PloS One
Michael S Nahorski, Laurence Seabra, Ania Straatman-Iwanowska, Aileen Wingenfeld, Anne Reiman, Xiaohong Lu, Jeff A Klomp, Bin T Teh, Mechthild Hatzfeld, Paul Gissen, Eamonn R Maher
Inherited mutations in the folliculin (FLCN) gene cause the Birt-Hogg-Dubé syndrome of familial hair follicle tumours (fibrofolliculomas), lung cysts and kidney tumours. Though folliculin has features of a tumour suppressor, the precise function of the FLCN gene product is not well characterized. We identified plakophilin-4 (p0071) as a potential novel folliculin interacting protein by yeast two-hybrid analysis. We confirmed the interaction of folliculin with p0071 by co-immunoprecipitation studies and, in view of previous studies linking p0071 to the regulation of rho-signalling, cytokinesis and intercellular junction formation, we investigated the effect of cell folliculin status on p0071-related functions...
December 15, 2012: Human Molecular Genetics
Hidekazu Tanaka, Kazuaki Takafuji, Akihiko Taguchi, Pattama Wiriyasermkul, Ryuichi Ohgaki, Shushi Nagamori, Pann-Ghill Suh, Yoshikatsu Kanai
The CNS synapse is an adhesive junction differentiated for chemical neurotransmission and is equipped with presynaptic vesicles and postsynaptic neurotransmitter receptors. Cell adhesion molecule cadherins not only maintain connections between pre- and postsynaptic membranes but also modulate the efficacy of synaptic transmission. Although the components of the cadherin-mediated adhesive apparatus have been studied extensively in various cell systems, the complete picture of these components, particularly at the synaptic junction, remains elusive...
July 2012: Neurochemistry International
Tim Pieters, Jolanda van Hengel, Frans van Roy
p120 catenin (p120ctn), a component of the cadherin-catenin complex, was the first member to be identified in a most interesting subfamily of the Armadillo family. Several p120ctn isoforms are generated by alternative splicing. These isoforms fulfill pleiotropic functions according to their subcellular localization: modulating the turnover rate of membrane-bound cadherins, regulating the activation of small Rho GTPases in the cytoplasm, and modulating nuclear transcription. Over the last two decades, knowledge of p120ctn has grown remarkably, and this has been achieved in part by using different animal models...
2012: Frontiers in Bioscience (Landmark Edition)
Kyucheol Cho, Moonsup Lee, Dongmin Gu, William A Munoz, Hong Ji, Malgorzata Kloc, Pierre D McCrea
The novel adaptor protein Kazrin associates with multifunctional entities including p120-subfamily members (ARVCF-, delta-, and p0071-catenin). Critical contributions of Kazrin to development or homeostasis are indicated with respect to ectoderm formation, integrity and keratinocyte differentiation, whereas its presence in varied tissues suggests broader roles. We find that Kazrin is maternally loaded, is expressed across development and becomes enriched in the forming head. Kazrin's potential contributions to craniofacial development were probed by means of knockdown in the prospective anterior neural region...
December 2011: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Ana Maria Abreu-Velez, Michael S Howard, Hong Yi, Weiqing Gao, Takashi Hashimoto, Hans E Grossniklaus
BACKGROUND: Endemic pemphigus foliaceus (EPF), is also known as "fogo selvagem" or "wild fire," reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). METHODS: We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area...
June 2011: Journal of Clinical Immunology
Robert H Carnahan, Antonis Rokas, Eric A Gaucher, Albert B Reynolds
BACKGROUND: p120-catenin (p120) is the prototypical member of a subclass of armadillo-related proteins that includes δ-catenin/NPRAP, ARVCF, p0071, and the more distantly related plakophilins 1-3. In vertebrates, p120 is essential in regulating surface expression and stability of all classical cadherins, and directly interacts with Kaiso, a BTB/ZF family transcription factor. METHODOLOGY/PRINCIPAL FINDINGS: To clarify functional relationships between these proteins and how they relate to the classical cadherins, we have examined the proteomes of 14 diverse vertebrate and metazoan species...
2010: PloS One
Kyucheol Cho, Travis G Vaught, Hong Ji, Dongmin Gu, Catherine Papasakelariou-Yared, Nicola Horstmann, Jean Marie Jennings, Moonsup Lee, Lisa M Sevilla, Malgorzata Kloc, Albert B Reynolds, Fiona M Watt, Richard G Brennan, Andrew P Kowalczyk, Pierre D McCrea
In common with other p120-catenin subfamily members, Xenopus ARVCF (xARVCF) binds cadherin cytoplasmic domains to enhance cadherin metabolic stability or, when dissociated, modulates Rho-family GTPases. We report here that xARVCF binds and is stabilized by Xenopus KazrinA (xKazrinA), a widely expressed conserved protein that bears little homology to established protein families, and which is known to influence keratinocyte proliferation and differentiation and cytoskeletal activity. Although we found that xKazrinA binds directly to xARVCF, we did not resolve xKazrinA within a larger ternary complex with cadherin, nor did it co-precipitate with core desmosomal components...
December 1, 2010: Journal of Cell Science
Steffen Rickelt, Stefania Rizzo, Yvette Doerflinger, Hanswalter Zentgraf, Cristina Basso, Gino Gerosa, Gaetano Thiene, Roland Moll, Werner W Franke
Using novel antibodies of high avidity to--and specificity for--the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by α- and β-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF...
November 2010: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Britta Walter, Ulrike Krebs, Irina Berger, Ilse Hofmann
Protein p0071 is a member of the p120-subfamily of armadillo proteins and is well known as a junctional plaque component involved in cell-cell adhesion, especially in adherens junctions. By systematic immunohistochemical analysis of mouse and human kidney tissues, p0071 was prominently detected in distinct kidney tubules. Upon double-labeling immunolocalization experiments with segment-specific markers, p0071 was predominantly localized in distal straight and convoluted tubules and to a lesser extent in proximal tubules, in the ascending thin limb of loop of Henle and in the collecting ducts...
January 2010: Histochemistry and Cell Biology
Nina Stenzel, Christian P Fetzer, Rolf Heumann, Kai S Erdmann
Multi-PDZ (PSD-95/Discs large/Zonula-occludens-1) domain proteins play a crucial role in the establishment and maintenance of cell polarization. The novel multi-PDZ domain protein FRMPD2 is a potential scaffolding protein consisting of an N-terminal KIND domain, a FERM domain and three PDZ domains. Here we show that FRMPD2 is localized in a polarized fashion in epithelial cells at the basolateral membrane and partially colocalizes with the tight-junction marker protein Zonula-occludens-1. Downregulation of FRMPD2 protein in Caco-2 cells is associated with an impairment of tight junction formation...
September 15, 2009: Journal of Cell Science
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