Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-cadherin
Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial c...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (25), p.14979-14984 |
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creator | Wu, Shaoguang Lim, Kuei-Cheng Huang, Julie Saidi, Roxan F. Sears, Cynthia L. |
description | Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin. |
doi_str_mv | 10.1073/pnas.95.25.14979 |
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BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.25.14979</identifier><identifier>PMID: 9844001</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Actins ; Antibodies ; Bacteroides fragilis ; Bacteroides fragilis - metabolism ; Biological Sciences ; Cadherins ; Cadherins - metabolism ; Cell Adhesion ; Cell lines ; Cell membranes ; Cellular immunity ; Enterotoxins - metabolism ; Epithelial cells ; Humans ; L cells ; Metalloendopeptidases - metabolism ; Microscopy ; Toxins</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-12, Vol.95 (25), p.14979-14984</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright © 1998, The National Academy of Sciences 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-13af9acf4033743d5a7e849cc88af8f86d06cb76f94667baca4b039520b20b533</citedby><cites>FETCH-LOGICAL-c496t-13af9acf4033743d5a7e849cc88af8f86d06cb76f94667baca4b039520b20b533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/95/25.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/46655$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/46655$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9844001$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Shaoguang</creatorcontrib><creatorcontrib>Lim, Kuei-Cheng</creatorcontrib><creatorcontrib>Huang, Julie</creatorcontrib><creatorcontrib>Saidi, Roxan F.</creatorcontrib><creatorcontrib>Sears, Cynthia L.</creatorcontrib><title>Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-cadherin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.</description><subject>Actins</subject><subject>Antibodies</subject><subject>Bacteroides fragilis</subject><subject>Bacteroides fragilis - metabolism</subject><subject>Biological Sciences</subject><subject>Cadherins</subject><subject>Cadherins - metabolism</subject><subject>Cell Adhesion</subject><subject>Cell lines</subject><subject>Cell membranes</subject><subject>Cellular immunity</subject><subject>Enterotoxins - metabolism</subject><subject>Epithelial cells</subject><subject>Humans</subject><subject>L cells</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Microscopy</subject><subject>Toxins</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEUx4Moda3eRRDnJB6c9WXyG7zUZW2Fgj3oxUvIZDLdlNlkTTKl_vfOuMvSXiw8ePC-n-_jJV-EXmNYYhDk0y6YvFRs2bAlpkqoJ2iBQeGaUwVP0QKgEbWkDX2OXuR8AwCKSThBJ0pSCoAX6OqLscWl6DuXqz6Zaz_4XK3DPCvxzodqNThzO4ll46pfMYyDqc66jUsu5OpqgpwPH6t1bc089OEletabIbtXh36Kfn5d_1hd1Jffz7-tzi5rSxUvNSamV8b2FAgRlHTMCCepslZK08te8g64bQXvFeVctMYa2gJRrIF2KkbIKfq837sb263rrAslmUHvkt-a9EdH4_VDJfiNvo63uqGM48n-_mBP8ffoctFbn60bBhNcHLMWgHGjGH0UxAJTyfkMwh60KeacXH-8BYOew9JzWFox3TD9L6zJ8vb-G46GQzqT_u6gz86j-mDDh_8Tuh-Hobi7MqFv9uhNLjEd2el7GSN_AXXUs0E</recordid><startdate>19981208</startdate><enddate>19981208</enddate><creator>Wu, Shaoguang</creator><creator>Lim, Kuei-Cheng</creator><creator>Huang, Julie</creator><creator>Saidi, Roxan F.</creator><creator>Sears, Cynthia L.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>The National Academy of Sciences</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>7QL</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19981208</creationdate><title>Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-cadherin</title><author>Wu, Shaoguang ; Lim, Kuei-Cheng ; Huang, Julie ; Saidi, Roxan F. ; Sears, Cynthia L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-13af9acf4033743d5a7e849cc88af8f86d06cb76f94667baca4b039520b20b533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Actins</topic><topic>Antibodies</topic><topic>Bacteroides fragilis</topic><topic>Bacteroides fragilis - metabolism</topic><topic>Biological Sciences</topic><topic>Cadherins</topic><topic>Cadherins - metabolism</topic><topic>Cell Adhesion</topic><topic>Cell lines</topic><topic>Cell membranes</topic><topic>Cellular immunity</topic><topic>Enterotoxins - metabolism</topic><topic>Epithelial cells</topic><topic>Humans</topic><topic>L cells</topic><topic>Metalloendopeptidases - metabolism</topic><topic>Microscopy</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Shaoguang</creatorcontrib><creatorcontrib>Lim, Kuei-Cheng</creatorcontrib><creatorcontrib>Huang, Julie</creatorcontrib><creatorcontrib>Saidi, Roxan F.</creatorcontrib><creatorcontrib>Sears, Cynthia L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Shaoguang</au><au>Lim, Kuei-Cheng</au><au>Huang, Julie</au><au>Saidi, Roxan F.</au><au>Sears, Cynthia L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-cadherin</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1998-12-08</date><risdate>1998</risdate><volume>95</volume><issue>25</issue><spage>14979</spage><epage>14984</epage><pages>14979-14984</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>9844001</pmid><doi>10.1073/pnas.95.25.14979</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
subjects | Actins Antibodies Bacteroides fragilis Bacteroides fragilis - metabolism Biological Sciences Cadherins Cadherins - metabolism Cell Adhesion Cell lines Cell membranes Cellular immunity Enterotoxins - metabolism Epithelial cells Humans L cells Metalloendopeptidases - metabolism Microscopy Toxins |
title | Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-cadherin |
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