Publicação
LAMP2A regulates the loading of proteins into exosomes
| Resumo: | Exosomes are extracellular vesicles of endosomal origin that are released by practically all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs, and proteins between different cells, tissues, or organs. Here, we describe a mechanism whereby proteins containing a KFERQ motif pentapeptide are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, we demonstrate that this mechanism is independent of the ESCRT machinery but dependent on HSC70, CD63, Alix, Syntenin-1, Rab31, and ceramides. We show that the master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. In addition, by tagging fluorescent proteins with KFERQ-like sequences, we were able to follow the interorgan transfer of exosomes. Our findings open new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs. |
|---|---|
| Autores principais: | Ferreira, João Vasco |
| Outros Autores: | da Rosa Soares, Ana; Ramalho, José; Máximo Carvalho, Catarina; Cardoso, Maria Helena; Pintado, Petra; Carvalho, Ana Sofia; Beck, Hans Christian; Matthiesen, Rune; Matthiesen, Rune; Zuzarte, Mónica; Girão, Henrique; van Niel, Guillaume; Pereira, Paulo |
| Assunto: | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983998265425920 |
|---|---|
| author | Ferreira, João Vasco |
| author2 | da Rosa Soares, Ana Ramalho, José Máximo Carvalho, Catarina Cardoso, Maria Helena Pintado, Petra Carvalho, Ana Sofia Beck, Hans Christian Matthiesen, Rune Matthiesen, Rune Zuzarte, Mónica Girão, Henrique van Niel, Guillaume Pereira, Paulo |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Ferreira, João Vasco da Rosa Soares, Ana Ramalho, José Máximo Carvalho, Catarina Cardoso, Maria Helena Pintado, Petra Carvalho, Ana Sofia Beck, Hans Christian Matthiesen, Rune Matthiesen, Rune Zuzarte, Mónica Girão, Henrique van Niel, Guillaume Pereira, Paulo |
| author_role | author |
| contributor_name_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) American Association for the Advancement of Science RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Ferreira, João Vasco\"},{\"Person.name\":\"da Rosa Soares, Ana\"},{\"Person.name\":\"Ramalho, José\"},{\"Person.name\":\"Máximo Carvalho, Catarina\"},{\"Person.name\":\"Cardoso, Maria Helena\"},{\"Person.name\":\"Pintado, Petra\"},{\"Person.name\":\"Carvalho, Ana Sofia\"},{\"Person.name\":\"Beck, Hans Christian\"},{\"Person.name\":\"Matthiesen, Rune\"},{\"Person.name\":\"Matthiesen, Rune\",\"Person.identifier.orcid\":\"0000-0002-6353-2616\"},{\"Person.name\":\"Zuzarte, Mónica\"},{\"Person.name\":\"Girão, Henrique\"},{\"Person.name\":\"van Niel, Guillaume\"},{\"Person.name\":\"Pereira, Paulo\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) American Association for the Advancement of Science RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Ferreira, João Vasco da Rosa Soares, Ana Ramalho, José Máximo Carvalho, Catarina Cardoso, Maria Helena Pintado, Petra Carvalho, Ana Sofia Beck, Hans Christian Matthiesen, Rune Matthiesen, Rune Zuzarte, Mónica Girão, Henrique van Niel, Guillaume Pereira, Paulo |
| datacite.date.Accepted.fl_str_mv | 2022-03-25T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-04-05T22:57:06Z |
| datacite.date.embargoed.fl_str_mv | 2022-04-05T22:57:06Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| datacite.titles.title.fl_str_mv | LAMP2A regulates the loading of proteins into exosomes |
| dc.contributor.none.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) American Association for the Advancement of Science RUN |
| dc.creator.none.fl_str_mv | Ferreira, João Vasco da Rosa Soares, Ana Ramalho, José Máximo Carvalho, Catarina Cardoso, Maria Helena Pintado, Petra Carvalho, Ana Sofia Beck, Hans Christian Matthiesen, Rune Matthiesen, Rune Zuzarte, Mónica Girão, Henrique van Niel, Guillaume Pereira, Paulo |
| dc.date.Accepted.fl_str_mv | 2022-03-25T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-04-05T22:57:06Z |
| dc.date.embargoed.fl_str_mv | 2022-04-05T22:57:06Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/135926 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| dc.title.fl_str_mv | LAMP2A regulates the loading of proteins into exosomes |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Exosomes are extracellular vesicles of endosomal origin that are released by practically all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs, and proteins between different cells, tissues, or organs. Here, we describe a mechanism whereby proteins containing a KFERQ motif pentapeptide are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, we demonstrate that this mechanism is independent of the ESCRT machinery but dependent on HSC70, CD63, Alix, Syntenin-1, Rab31, and ceramides. We show that the master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. In addition, by tagging fluorescent proteins with KFERQ-like sequences, we were able to follow the interorgan transfer of exosomes. Our findings open new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/527a4a13-dfa6-4613-86d5-f132b5f6f48e/download |
| id | run_b49ce00fc99d2012e0aa83dd8aeb6cef |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/135926 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/135926 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Ferreira, João Vasco da Rosa Soares, Ana Ramalho, José Máximo Carvalho, Catarina Cardoso, Maria Helena Pintado, Petra Carvalho, Ana Sofia Beck, Hans Christian Matthiesen, Rune Matthiesen, Rune Matthiesen, Rune https://www.ciencia-id.pt/BB1A-A606-EE77 BB1A-A606-EE77 http://orcid.org/0000-0002-6353-2616 0000-0002-6353-2616 Zuzarte, Mónica Girão, Henrique van Niel, Guillaume Pereira, Paulo |
| publishDate | 2022 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenExosomes are extracellular vesicles of endosomal origin that are released by practically all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs, and proteins between different cells, tissues, or organs. Here, we describe a mechanism whereby proteins containing a KFERQ motif pentapeptide are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, we demonstrate that this mechanism is independent of the ESCRT machinery but dependent on HSC70, CD63, Alix, Syntenin-1, Rab31, and ceramides. We show that the master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. In addition, by tagging fluorescent proteins with KFERQ-like sequences, we were able to follow the interorgan transfer of exosomes. Our findings open new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.application/pdfenLAMP2A regulates the loading of proteins into exosomesFerreira, João Vascoda Rosa Soares, AnaRamalho, JoséMáximo Carvalho, CatarinaCardoso, Maria HelenaPintado, PetraCarvalho, Ana SofiaBeck, Hans ChristianMatthiesen, RunePersonalMatthiesen, RuneDSpacehttp://dspace.org/items/67181d3c-b83e-4151-9a74-0ea14aeb7f05DSpacehttp://dspace.org/items/67181d3c-b83e-4151-9a74-0ea14aeb7f05MatthiesenRuneCiência IDhttps://www.ciencia-id.ptBB1A-A606-EE77ORCIDhttp://orcid.org0000-0002-6353-2616Scopus Author IDhttps://www.scopus.com9741897800Zuzarte, MónicaGirão, Henriquevan Niel, GuillaumePereira, PauloNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)American Association for the Advancement of ScienceHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2375-2548URNIsPartOfPURE: 42836010URNIsPartOfPURE UUID: 111c81a1-5f85-4b59-81f9-345d596ee624URNIsPartOfPubMed: 35333565URNIsPartOfScopus: 85127258740URNIsPartOfWOS: 000800334900009URNIsPartOfORCID: /0000-0002-9908-2290/work/151406796DOIIsPartOf10.1126/sciadv.abm11402022-04-05T22:57:06Z2022-03-252022-03-25T00:00:00ZHandlehttp://hdl.handle.net/10362/135926http://purl.org/coar/access_right/c_abf2open accessEXTRACELLULAR VESICLEDEGRADATIONBIOGENESISSYNTENINLYSOSOMESSECRETION4283740 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/527a4a13-dfa6-4613-86d5-f132b5f6f48e/download |
| spellingShingle | LAMP2A regulates the loading of proteins into exosomes Ferreira, João Vasco EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| status | SINGLETON |
| subject.fl_str_mv | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| title | LAMP2A regulates the loading of proteins into exosomes |
| title_full | LAMP2A regulates the loading of proteins into exosomes |
| title_fullStr | LAMP2A regulates the loading of proteins into exosomes |
| title_full_unstemmed | LAMP2A regulates the loading of proteins into exosomes |
| title_short | LAMP2A regulates the loading of proteins into exosomes |
| title_sort | LAMP2A regulates the loading of proteins into exosomes |
| topic | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| topic_facet | EXTRACELLULAR VESICLE DEGRADATION BIOGENESIS SYNTENIN LYSOSOMES SECRETION |
| url | http://hdl.handle.net/10362/135926 |
| visible | 1 |