Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation
Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood....
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| Veröffentlicht in: | PloS one 2010-08, Vol.5 (8), p.e12246 |
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| creator | Barone, Maria Vittoria Nanayakkara, Merlin Paolella, Giovanni Maglio, Mariantonia Vitale, Virginia Troiano, Raffaele Ribecco, Maria Teresa Silvia Lania, Giuliana Zanzi, Delia Santagata, Sara Auricchio, Renata Troncone, Riccardo Auricchio, Salvatore |
| description | Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles.
Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy.
P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies. |
| doi_str_mv | 10.1371/journal.pone.0012246 |
| format | Article |
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Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy.
P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0012246</identifier><identifier>PMID: 20805894</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Activation ; Amino Acid Sequence ; Analysis ; Animals ; Apoptosis ; Autoimmune diseases ; Biopsy ; Caco-2 Cells ; Celiac disease ; Cell Biology/Membranes and Sorting ; Cell Cycle ; Cell lines ; Endocytosis ; Endosomal Sorting Complexes Required for Transport - chemistry ; Endosomal Sorting Complexes Required for Transport - metabolism ; Endosomes ; Endosomes - metabolism ; Enterocytes ; Enterocytes - metabolism ; Epidermal growth factor ; Epidermal growth factor receptors ; Epidermal growth factors ; ErbB Receptors - metabolism ; Fluorophores ; Food ; Gastroenterology and Hepatology/Small Intestine ; Gliadin ; Gliadin - chemistry ; Gliadin - metabolism ; Gluten ; Humans ; Immunity ; Immunofluorescence ; Immunogenicity ; Immunology/Innate Immunity ; Innate immunity ; Intestine ; Intestine, Small - pathology ; Kinases ; Laboratories ; Localization ; Maturation ; Membranes ; Metabolism ; Mice ; Microscopy ; Molecular Sequence Data ; Muscle proteins ; Pediatrics ; Peptide Fragments - chemistry ; Peptide Fragments - metabolism ; Peptides ; Phosphoproteins - chemistry ; Phosphoproteins - metabolism ; Protein Transport ; Proteins ; Rats ; Small intestine ; Transport Vesicles - metabolism ; Triticum aestivum ; Vesicles ; Wheat</subject><ispartof>PloS one, 2010-08, Vol.5 (8), p.e12246</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Barone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Barone et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-1c392b66a68d8737e9b1b8eb92c6de3eb40b15afd88c76ecbdba136354a2e2723</citedby><cites>FETCH-LOGICAL-c723t-1c392b66a68d8737e9b1b8eb92c6de3eb40b15afd88c76ecbdba136354a2e2723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923621/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923621/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20805894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bassham, Diane</contributor><creatorcontrib>Barone, Maria Vittoria</creatorcontrib><creatorcontrib>Nanayakkara, Merlin</creatorcontrib><creatorcontrib>Paolella, Giovanni</creatorcontrib><creatorcontrib>Maglio, Mariantonia</creatorcontrib><creatorcontrib>Vitale, Virginia</creatorcontrib><creatorcontrib>Troiano, Raffaele</creatorcontrib><creatorcontrib>Ribecco, Maria Teresa Silvia</creatorcontrib><creatorcontrib>Lania, Giuliana</creatorcontrib><creatorcontrib>Zanzi, Delia</creatorcontrib><creatorcontrib>Santagata, Sara</creatorcontrib><creatorcontrib>Auricchio, Renata</creatorcontrib><creatorcontrib>Troncone, Riccardo</creatorcontrib><creatorcontrib>Auricchio, Salvatore</creatorcontrib><title>Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles.
Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy.
P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies.</description><subject>Actin</subject><subject>Activation</subject><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autoimmune diseases</subject><subject>Biopsy</subject><subject>Caco-2 Cells</subject><subject>Celiac disease</subject><subject>Cell Biology/Membranes and Sorting</subject><subject>Cell Cycle</subject><subject>Cell lines</subject><subject>Endocytosis</subject><subject>Endosomal Sorting Complexes Required for Transport - chemistry</subject><subject>Endosomal Sorting Complexes Required for Transport - metabolism</subject><subject>Endosomes</subject><subject>Endosomes - metabolism</subject><subject>Enterocytes</subject><subject>Enterocytes - metabolism</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Epidermal growth factors</subject><subject>ErbB Receptors - metabolism</subject><subject>Fluorophores</subject><subject>Food</subject><subject>Gastroenterology and Hepatology/Small Intestine</subject><subject>Gliadin</subject><subject>Gliadin - chemistry</subject><subject>Gliadin - metabolism</subject><subject>Gluten</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunofluorescence</subject><subject>Immunogenicity</subject><subject>Immunology/Innate Immunity</subject><subject>Innate immunity</subject><subject>Intestine</subject><subject>Intestine, Small - pathology</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Localization</subject><subject>Maturation</subject><subject>Membranes</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Molecular Sequence Data</subject><subject>Muscle proteins</subject><subject>Pediatrics</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptides</subject><subject>Phosphoproteins - chemistry</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Rats</subject><subject>Small intestine</subject><subject>Transport Vesicles - metabolism</subject><subject>Triticum aestivum</subject><subject>Vesicles</subject><subject>Wheat</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQgJx2MVf6zgXpKqCslKlIr4uHCzHnux65Y1T2yn03-Nl02qDekA-2B4_8449nimK5xjNMa3wu40fQqfcvPcdzBHChDD-oDjGNSUzThB9eLA-Kp7EuEFoQQXnj4sjggRaiJodFz_PnVXGdmUPfbIGys8UzxgtndfK2QixTL6Eznh9k6wuryFa7bJVdaa0XYLQQsjbXzaty7QGG8qtSkNQyfruafGoVS7Cs3E-Kb5__PDt7NPs4vJ8eXZ6MdMVoWmGNa1Jw7niwoiKVlA3uBHQ1ERzAxQahhq8UK0RQlccdGMahSmnC6YIkCxxUrzc6_bORznmJUpMsagpQwhlYrknjFcb2Qe7VeFGemXlX4MPK6lC2r1MIsxwhRBjFaKMsVpUpkHCtDQvECIia70fow3NFoyGLgXlJqLTk86u5cpfS1ITygnOAm9GgeCvBohJbm3U4JzqwA9RVpyQ_D2cZ_LVP-T9jxuplcr3t13rc1i905SnrMr3XlBUZ2p-D5WHga3VuYZam-0Th7cTh8wk-J1WaohRLr9--X_28seUfX3ArkG5tI7eDbuKiVOQ7UEdfIwB2rscYyR3LXCbDblrATm2QHZ7cfg_d063NU__AGAF_4Y</recordid><startdate>20100818</startdate><enddate>20100818</enddate><creator>Barone, Maria Vittoria</creator><creator>Nanayakkara, Merlin</creator><creator>Paolella, Giovanni</creator><creator>Maglio, Mariantonia</creator><creator>Vitale, Virginia</creator><creator>Troiano, Raffaele</creator><creator>Ribecco, Maria Teresa Silvia</creator><creator>Lania, Giuliana</creator><creator>Zanzi, Delia</creator><creator>Santagata, Sara</creator><creator>Auricchio, Renata</creator><creator>Troncone, Riccardo</creator><creator>Auricchio, Salvatore</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100818</creationdate><title>Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation</title><author>Barone, Maria Vittoria ; Nanayakkara, Merlin ; Paolella, Giovanni ; Maglio, Mariantonia ; Vitale, Virginia ; Troiano, Raffaele ; Ribecco, Maria Teresa Silvia ; Lania, Giuliana ; Zanzi, Delia ; Santagata, Sara ; Auricchio, Renata ; Troncone, Riccardo ; Auricchio, Salvatore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-1c392b66a68d8737e9b1b8eb92c6de3eb40b15afd88c76ecbdba136354a2e2723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Actin</topic><topic>Activation</topic><topic>Amino Acid Sequence</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autoimmune diseases</topic><topic>Biopsy</topic><topic>Caco-2 Cells</topic><topic>Celiac disease</topic><topic>Cell Biology/Membranes and Sorting</topic><topic>Cell Cycle</topic><topic>Cell lines</topic><topic>Endocytosis</topic><topic>Endosomal Sorting Complexes Required for Transport - chemistry</topic><topic>Endosomal Sorting Complexes Required for Transport - metabolism</topic><topic>Endosomes</topic><topic>Endosomes - metabolism</topic><topic>Enterocytes</topic><topic>Enterocytes - metabolism</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Epidermal growth factors</topic><topic>ErbB Receptors - metabolism</topic><topic>Fluorophores</topic><topic>Food</topic><topic>Gastroenterology and Hepatology/Small Intestine</topic><topic>Gliadin</topic><topic>Gliadin - chemistry</topic><topic>Gliadin - metabolism</topic><topic>Gluten</topic><topic>Humans</topic><topic>Immunity</topic><topic>Immunofluorescence</topic><topic>Immunogenicity</topic><topic>Immunology/Innate Immunity</topic><topic>Innate immunity</topic><topic>Intestine</topic><topic>Intestine, Small - pathology</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Localization</topic><topic>Maturation</topic><topic>Membranes</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Molecular Sequence Data</topic><topic>Muscle proteins</topic><topic>Pediatrics</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptides</topic><topic>Phosphoproteins - chemistry</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>Rats</topic><topic>Small intestine</topic><topic>Transport Vesicles - metabolism</topic><topic>Triticum aestivum</topic><topic>Vesicles</topic><topic>Wheat</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barone, Maria Vittoria</creatorcontrib><creatorcontrib>Nanayakkara, Merlin</creatorcontrib><creatorcontrib>Paolella, Giovanni</creatorcontrib><creatorcontrib>Maglio, Mariantonia</creatorcontrib><creatorcontrib>Vitale, Virginia</creatorcontrib><creatorcontrib>Troiano, Raffaele</creatorcontrib><creatorcontrib>Ribecco, Maria Teresa Silvia</creatorcontrib><creatorcontrib>Lania, Giuliana</creatorcontrib><creatorcontrib>Zanzi, Delia</creatorcontrib><creatorcontrib>Santagata, Sara</creatorcontrib><creatorcontrib>Auricchio, Renata</creatorcontrib><creatorcontrib>Troncone, Riccardo</creatorcontrib><creatorcontrib>Auricchio, Salvatore</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barone, Maria Vittoria</au><au>Nanayakkara, Merlin</au><au>Paolella, Giovanni</au><au>Maglio, Mariantonia</au><au>Vitale, Virginia</au><au>Troiano, Raffaele</au><au>Ribecco, Maria Teresa Silvia</au><au>Lania, Giuliana</au><au>Zanzi, Delia</au><au>Santagata, Sara</au><au>Auricchio, Renata</au><au>Troncone, Riccardo</au><au>Auricchio, Salvatore</au><au>Bassham, Diane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-08-18</date><risdate>2010</risdate><volume>5</volume><issue>8</issue><spage>e12246</spage><pages>e12246-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles.
Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy.
P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20805894</pmid><doi>10.1371/journal.pone.0012246</doi><tpages>e12246</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-08, Vol.5 (8), p.e12246 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1318934000 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Actin Activation Amino Acid Sequence Analysis Animals Apoptosis Autoimmune diseases Biopsy Caco-2 Cells Celiac disease Cell Biology/Membranes and Sorting Cell Cycle Cell lines Endocytosis Endosomal Sorting Complexes Required for Transport - chemistry Endosomal Sorting Complexes Required for Transport - metabolism Endosomes Endosomes - metabolism Enterocytes Enterocytes - metabolism Epidermal growth factor Epidermal growth factor receptors Epidermal growth factors ErbB Receptors - metabolism Fluorophores Food Gastroenterology and Hepatology/Small Intestine Gliadin Gliadin - chemistry Gliadin - metabolism Gluten Humans Immunity Immunofluorescence Immunogenicity Immunology/Innate Immunity Innate immunity Intestine Intestine, Small - pathology Kinases Laboratories Localization Maturation Membranes Metabolism Mice Microscopy Molecular Sequence Data Muscle proteins Pediatrics Peptide Fragments - chemistry Peptide Fragments - metabolism Peptides Phosphoproteins - chemistry Phosphoproteins - metabolism Protein Transport Proteins Rats Small intestine Transport Vesicles - metabolism Triticum aestivum Vesicles Wheat |
| title | Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation |
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