Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER
Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell...
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| Veröffentlicht in: | JOURNAL OF CELL BIOLOGY 2016-04, Vol.213 (2), p.173-184 |
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| creator | Heusermann, Wolf Hean, Justin Trojer, Dominic Steib, Emmanuelle von Bueren, Stefan Graff-Meyer, Alexandra Genoud, Christel Martin, Katrin Pizzato, Nicolas Voshol, Johannes Morrissey, David V Andaloussi, Samir E L Wood, Matthew J Meisner-Kober, Nicole C |
| description | Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery. |
| doi_str_mv | 10.1083/jcb.201506084 |
| format | Article |
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Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201506084</identifier><identifier>PMID: 27114500</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Bacteria ; Biological Transport ; Cells ; Endoplasmic Reticulum - metabolism ; Endoplasmic Reticulum - ultrastructure ; Endosomes - metabolism ; Endosomes - ultrastructure ; Exosomes - metabolism ; Exosomes - physiology ; Exosomes - ultrastructure ; HEK293 Cells ; Humans ; Lipids ; Microscopy, Electron, Scanning ; Pseudopodia - physiology ; Pseudopodia - ultrastructure ; Ribonucleic acid ; RNA ; Signal transduction</subject><ispartof>JOURNAL OF CELL BIOLOGY, 2016-04, Vol.213 (2), p.173-184</ispartof><rights>2016 Heusermann et al.</rights><rights>Copyright Rockefeller University Press Apr 25, 2016</rights><rights>2016 Heusermann et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-986e0dc7dc6abb9c8d8b48c96a47b36028581134951d93f38cd6644ba2ce3ea13</citedby><cites>FETCH-LOGICAL-c519t-986e0dc7dc6abb9c8d8b48c96a47b36028581134951d93f38cd6644ba2ce3ea13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27114500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:133525581$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Heusermann, Wolf</creatorcontrib><creatorcontrib>Hean, Justin</creatorcontrib><creatorcontrib>Trojer, Dominic</creatorcontrib><creatorcontrib>Steib, Emmanuelle</creatorcontrib><creatorcontrib>von Bueren, Stefan</creatorcontrib><creatorcontrib>Graff-Meyer, Alexandra</creatorcontrib><creatorcontrib>Genoud, Christel</creatorcontrib><creatorcontrib>Martin, Katrin</creatorcontrib><creatorcontrib>Pizzato, Nicolas</creatorcontrib><creatorcontrib>Voshol, Johannes</creatorcontrib><creatorcontrib>Morrissey, David V</creatorcontrib><creatorcontrib>Andaloussi, Samir E L</creatorcontrib><creatorcontrib>Wood, Matthew J</creatorcontrib><creatorcontrib>Meisner-Kober, Nicole C</creatorcontrib><title>Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER</title><title>JOURNAL OF CELL BIOLOGY</title><addtitle>J Cell Biol</addtitle><description>Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.</description><subject>Bacteria</subject><subject>Biological Transport</subject><subject>Cells</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Endoplasmic Reticulum - ultrastructure</subject><subject>Endosomes - metabolism</subject><subject>Endosomes - ultrastructure</subject><subject>Exosomes - metabolism</subject><subject>Exosomes - physiology</subject><subject>Exosomes - ultrastructure</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Lipids</subject><subject>Microscopy, Electron, Scanning</subject><subject>Pseudopodia - physiology</subject><subject>Pseudopodia - ultrastructure</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal transduction</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpdkstvEzEQxi0EoqFw5IosceHQLX4_LkioCg-pEhKCs-W1vY3DZh1sb0v_e7xtCJST7ZnffJpvPAC8xOgcI0Xfbl1_ThDmSCDFHoEV5gx1CjP0GKwQIrjTnPAT8KyULUKISUafghMiMWYcoRW4Xv9KJe1CgWXOA0wTHOKY9slHC2uCYaohQxfGsUBb29Mnd1ujg5tUYdmnWs5gzXYYWugm1k2c7pg7xTNoJw9tDrDafBVq8Iti3QS4_vocPBnsWMKLw3kKvn9Yf7v41F1--fj54v1l5zjWtdNKBOSd9E7YvtdOedUz5bSwTPZUIKK4wpgyzbHXdKDKeSEY6y1xgQaL6Sno7nXLTdjPvdnnuLP51iQbzSH0o92C4YgLsvDv7vmW2QXvmv9sxwdlDzNT3JirdN3qFSNCN4E3B4Gcfs6hVLOLZZmfnUKai8FSccmYJLKhr_9Dt2nOUxvHQknNsBLyrwOXUyk5DMdmMDLLBpi2Aea4AY1_9a-DI_3ny-lvprOt5g</recordid><startdate>20160425</startdate><enddate>20160425</enddate><creator>Heusermann, Wolf</creator><creator>Hean, Justin</creator><creator>Trojer, Dominic</creator><creator>Steib, Emmanuelle</creator><creator>von Bueren, Stefan</creator><creator>Graff-Meyer, Alexandra</creator><creator>Genoud, Christel</creator><creator>Martin, Katrin</creator><creator>Pizzato, Nicolas</creator><creator>Voshol, Johannes</creator><creator>Morrissey, David V</creator><creator>Andaloussi, Samir E L</creator><creator>Wood, Matthew J</creator><creator>Meisner-Kober, Nicole C</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20160425</creationdate><title>Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER</title><author>Heusermann, Wolf ; 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Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. 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| subjects | Bacteria Biological Transport Cells Endoplasmic Reticulum - metabolism Endoplasmic Reticulum - ultrastructure Endosomes - metabolism Endosomes - ultrastructure Exosomes - metabolism Exosomes - physiology Exosomes - ultrastructure HEK293 Cells Humans Lipids Microscopy, Electron, Scanning Pseudopodia - physiology Pseudopodia - ultrastructure Ribonucleic acid RNA Signal transduction |
| title | Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER |
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