Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation
Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous st...
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| Veröffentlicht in: | Infection and Immunity 2006-05, Vol.74 (5), p.2613-2618 |
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| creator | Lerm, M Holm, A Seiron, A Särndahl, E Magnusson, K.-E Rasmusson, B |
| description | Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C[alpha]. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation. |
| doi_str_mv | 10.1128/IAI.74.5.2613-2618.2006 |
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The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C[alpha]. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.</description><identifier>ISSN: 1098-5522</identifier><identifier>ISSN: 0019-9567</identifier><identifier>EISSN: 1098-5522</identifier><identifier>DOI: 10.1128/IAI.74.5.2613-2618.2006</identifier><identifier>PMID: 16622197</identifier><identifier>CODEN: INFIBR</identifier><language>eng</language><publisher>Washington, DC: American Society for Microbiology</publisher><subject>Actins - analysis ; Actins - physiology ; Animals ; Biological and medical sciences ; cdc42 GTP-Binding Protein - physiology ; Cell Line ; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions ; Fundamental and applied biological sciences. Psychology ; Glycosphingolipids - physiology ; Leishmania donovani ; Leishmania donovani - physiology ; Lysosomal-Associated Membrane Protein 1 - metabolism ; MEDICIN ; MEDICINE ; Mice ; Microbiology ; Phagosomes - physiology ; Protein Kinase C-alpha - physiology ; Protein Transport ; rac1 GTP-Binding Protein - physiology</subject><ispartof>Infection and Immunity, 2006-05, Vol.74 (5), p.2613-2618</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright © 2006, American Society for Microbiology 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c568t-9ff4dd166ea86864a049cd4c2082e67df4ccb34dd02fccf540c6d31a584433fc3</citedby><cites>FETCH-LOGICAL-c568t-9ff4dd166ea86864a049cd4c2082e67df4ccb34dd02fccf540c6d31a584433fc3</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/PMC1459716/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459716/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,3192,3193,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17730678$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16622197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-35218$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lerm, M</creatorcontrib><creatorcontrib>Holm, A</creatorcontrib><creatorcontrib>Seiron, A</creatorcontrib><creatorcontrib>Särndahl, E</creatorcontrib><creatorcontrib>Magnusson, K.-E</creatorcontrib><creatorcontrib>Rasmusson, B</creatorcontrib><title>Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation</title><title>Infection and Immunity</title><addtitle>Infect Immun</addtitle><description>Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C[alpha]. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.</description><subject>Actins - analysis</subject><subject>Actins - physiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>cdc42 GTP-Binding Protein - physiology</subject><subject>Cell Line</subject><subject>Cellular Microbiology: Pathogen-Host Cell Molecular Interactions</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycosphingolipids - physiology</subject><subject>Leishmania donovani</subject><subject>Leishmania donovani - physiology</subject><subject>Lysosomal-Associated Membrane Protein 1 - metabolism</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Phagosomes - physiology</subject><subject>Protein Kinase C-alpha - physiology</subject><subject>Protein Transport</subject><subject>rac1 GTP-Binding Protein - physiology</subject><issn>1098-5522</issn><issn>0019-9567</issn><issn>1098-5522</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhSMEoqXwF2hYwIoEv2I7G6TRQOlIg6hKC0vr1nESoyRu7WQq_j1OM-pjhSxdX8nfPT72SZJjjHKMify0WW1ywfIiJxzTLBaZE4T4s-QQo1JmRUHI80f9QfIqhD8IYcaYfJkcYM4JwaU4TH5vjQ1tD4OFtHKD28UuPTc3k_UmpCfToEfrBujSdaUZSWGo0nPQOL1w6Zk3OzOM6VkLjQuuj9B3GCcP88Tr5EUNXTBv9vtRcnny9WJ9mm1_fNusV9tMF1yOWVnXrKqiHQOSS84AsVJXTBMkieGiqpnWVzQiiNRa1wVDmlcUQyEZo7TW9Cj5uOiGW3M9Xalrb3vwf5UDq77YXyvlfKM6OylaECwj_nnBI9ubSkf_HronU09PBtuqxu0UZkUpMI8CH_YC3t1MJoyqt0GbroPBuCkoLqQglP8fxAIzwe8UxQJq70Lwpr53g5Gaw1YxbCWYKtQc9lykmsOOk28fP-Zhbp9uBN7vAQgautrDoG144ISgKBqO3LuFa23T3sbkFYRe2fgZ99dG5nhhanAKGh91Ln8ShCnCSMSF6T8wSMhE</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Lerm, M</creator><creator>Holm, A</creator><creator>Seiron, A</creator><creator>Särndahl, E</creator><creator>Magnusson, K.-E</creator><creator>Rasmusson, B</creator><general>American Society for Microbiology</general><scope>FBQ</scope><scope>IQODW</scope><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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope></search><sort><creationdate>20060501</creationdate><title>Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation</title><author>Lerm, M ; Holm, A ; Seiron, A ; Särndahl, E ; Magnusson, K.-E ; Rasmusson, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c568t-9ff4dd166ea86864a049cd4c2082e67df4ccb34dd02fccf540c6d31a584433fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Actins - analysis</topic><topic>Actins - physiology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>cdc42 GTP-Binding Protein - physiology</topic><topic>Cell Line</topic><topic>Cellular Microbiology: Pathogen-Host Cell Molecular Interactions</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycosphingolipids - physiology</topic><topic>Leishmania donovani</topic><topic>Leishmania donovani - physiology</topic><topic>Lysosomal-Associated Membrane Protein 1 - metabolism</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Phagosomes - physiology</topic><topic>Protein Kinase C-alpha - physiology</topic><topic>Protein Transport</topic><topic>rac1 GTP-Binding Protein - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lerm, M</creatorcontrib><creatorcontrib>Holm, A</creatorcontrib><creatorcontrib>Seiron, A</creatorcontrib><creatorcontrib>Särndahl, E</creatorcontrib><creatorcontrib>Magnusson, K.-E</creatorcontrib><creatorcontrib>Rasmusson, B</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><jtitle>Infection and Immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lerm, M</au><au>Holm, A</au><au>Seiron, A</au><au>Särndahl, E</au><au>Magnusson, K.-E</au><au>Rasmusson, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation</atitle><jtitle>Infection and Immunity</jtitle><addtitle>Infect Immun</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>74</volume><issue>5</issue><spage>2613</spage><epage>2618</epage><pages>2613-2618</pages><issn>1098-5522</issn><issn>0019-9567</issn><eissn>1098-5522</eissn><coden>INFIBR</coden><abstract>Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C[alpha]. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>16622197</pmid><doi>10.1128/IAI.74.5.2613-2618.2006</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - analysis Actins - physiology Animals Biological and medical sciences cdc42 GTP-Binding Protein - physiology Cell Line Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Fundamental and applied biological sciences. Psychology Glycosphingolipids - physiology Leishmania donovani Leishmania donovani - physiology Lysosomal-Associated Membrane Protein 1 - metabolism MEDICIN MEDICINE Mice Microbiology Phagosomes - physiology Protein Kinase C-alpha - physiology Protein Transport rac1 GTP-Binding Protein - physiology |
| title | Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation |
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