Publicação
LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis
| Resumo: | The endolysosomal system maintains cellular homeostasis through protein degradation and the release of exosomes that mediate intercellular communication. LAMP2A, a transmembrane protein, has been implicated in selective cargo loading into exosomes, or eLLoC. Here, we investigated how LAMP2A influences endosomal protein composition and function using mass spectrometry of endosomal and exosomal fractions from human retinal pigment epithelial cells. Loss of LAMP2A changed Rab GTPase distribution, reduced cortical actin association, and shifted phosphoinositide dynamics, leading to enhanced endosomal acidification and maturation. These changes extended beyond the loss of proteins containing ExoSignals, the canonical targeting motifs, suggesting that LAMP2A contributes broadly to endosomal identity. Experimental validation confirmed that LAMP2A deficiency reprograms endosomal fate toward degradation while influencing exosome composition. These findings highlight a role for LAMP2A in coordinating membrane identity, endosomal maturation, and intercellular communication through exosomes, providing insights into mechanisms that couple endosomal remodeling with cellular signaling and clearance pathways. |
|---|---|
| Autores principais: | Ferreira, Joao Vasco |
| Outros Autores: | Ferraz, Luís Carvalho; da Rosa Soares, Ana; Ejtehadifar, Mostafa; Carvalho, Ana Sofia; Hall, Michael James; Morello, Judit; Beck, Hans Christian; Ramalho, Jose Silva; Matthiesen, Rune; Pereira, Paulo |
| Assunto: | Cell biology Molecular biology General |
| Ano: | 2026 |
| 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_ | 1868983766843654144 |
|---|---|
| author | Ferreira, Joao Vasco |
| author2 | Ferraz, Luís Carvalho da Rosa Soares, Ana Ejtehadifar, Mostafa Carvalho, Ana Sofia Hall, Michael James Morello, Judit Beck, Hans Christian Ramalho, Jose Silva Matthiesen, Rune Pereira, Paulo |
| author2_role | author author author author author author author author author author |
| author_facet | Ferreira, Joao Vasco Ferraz, Luís Carvalho da Rosa Soares, Ana Ejtehadifar, Mostafa Carvalho, Ana Sofia Hall, Michael James Morello, Judit Beck, Hans Christian Ramalho, Jose Silva Matthiesen, Rune Pereira, Paulo |
| author_role | author |
| contributor_name_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Elsevier RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Ferreira, Joao Vasco\"},{\"Person.name\":\"Ferraz, Luís Carvalho\"},{\"Person.name\":\"da Rosa Soares, Ana\"},{\"Person.name\":\"Ejtehadifar, Mostafa\"},{\"Person.name\":\"Carvalho, Ana Sofia\"},{\"Person.name\":\"Hall, Michael James\"},{\"Person.name\":\"Morello, Judit\"},{\"Person.name\":\"Beck, Hans Christian\"},{\"Person.name\":\"Ramalho, Jose Silva\"},{\"Person.name\":\"Matthiesen, Rune\"},{\"Person.name\":\"Pereira, Paulo\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Elsevier RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Ferreira, Joao Vasco Ferraz, Luís Carvalho da Rosa Soares, Ana Ejtehadifar, Mostafa Carvalho, Ana Sofia Hall, Michael James Morello, Judit Beck, Hans Christian Ramalho, Jose Silva Matthiesen, Rune Pereira, Paulo |
| datacite.date.Accepted.fl_str_mv | 2026-01-16T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-01-14T15:55:17Z |
| datacite.date.embargoed.fl_str_mv | 2026-01-14T15:55:17Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Cell biology Molecular biology General |
| datacite.titles.title.fl_str_mv | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| dc.contributor.none.fl_str_mv | iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Elsevier RUN |
| dc.creator.none.fl_str_mv | Ferreira, Joao Vasco Ferraz, Luís Carvalho da Rosa Soares, Ana Ejtehadifar, Mostafa Carvalho, Ana Sofia Hall, Michael James Morello, Judit Beck, Hans Christian Ramalho, Jose Silva Matthiesen, Rune Pereira, Paulo |
| dc.date.Accepted.fl_str_mv | 2026-01-16T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-01-14T15:55:17Z |
| dc.date.embargoed.fl_str_mv | 2026-01-14T15:55:17Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/199059 |
| 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 | Cell biology Molecular biology General |
| dc.title.fl_str_mv | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The endolysosomal system maintains cellular homeostasis through protein degradation and the release of exosomes that mediate intercellular communication. LAMP2A, a transmembrane protein, has been implicated in selective cargo loading into exosomes, or eLLoC. Here, we investigated how LAMP2A influences endosomal protein composition and function using mass spectrometry of endosomal and exosomal fractions from human retinal pigment epithelial cells. Loss of LAMP2A changed Rab GTPase distribution, reduced cortical actin association, and shifted phosphoinositide dynamics, leading to enhanced endosomal acidification and maturation. These changes extended beyond the loss of proteins containing ExoSignals, the canonical targeting motifs, suggesting that LAMP2A contributes broadly to endosomal identity. Experimental validation confirmed that LAMP2A deficiency reprograms endosomal fate toward degradation while influencing exosome composition. These findings highlight a role for LAMP2A in coordinating membrane identity, endosomal maturation, and intercellular communication through exosomes, providing insights into mechanisms that couple endosomal remodeling with cellular signaling and clearance pathways. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/09691016-82be-463c-8a75-a4f097a50b99/download |
| id | run_3ed4d04db9d4c8ae92d4515b41205ab9 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/199059 |
| 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:10362/199059 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Ferreira, Joao Vasco Ferraz, Luís Carvalho da Rosa Soares, Ana Ejtehadifar, Mostafa Carvalho, Ana Sofia Hall, Michael James Morello, Judit Beck, Hans Christian Ramalho, Jose Silva Matthiesen, Rune Pereira, Paulo |
| publishDate | 2026 |
| 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 | engenThe endolysosomal system maintains cellular homeostasis through protein degradation and the release of exosomes that mediate intercellular communication. LAMP2A, a transmembrane protein, has been implicated in selective cargo loading into exosomes, or eLLoC. Here, we investigated how LAMP2A influences endosomal protein composition and function using mass spectrometry of endosomal and exosomal fractions from human retinal pigment epithelial cells. Loss of LAMP2A changed Rab GTPase distribution, reduced cortical actin association, and shifted phosphoinositide dynamics, leading to enhanced endosomal acidification and maturation. These changes extended beyond the loss of proteins containing ExoSignals, the canonical targeting motifs, suggesting that LAMP2A contributes broadly to endosomal identity. Experimental validation confirmed that LAMP2A deficiency reprograms endosomal fate toward degradation while influencing exosome composition. These findings highlight a role for LAMP2A in coordinating membrane identity, endosomal maturation, and intercellular communication through exosomes, providing insights into mechanisms that couple endosomal remodeling with cellular signaling and clearance pathways.application/pdfenLAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesisFerreira, Joao VascoFerraz, Luís Carvalhoda Rosa Soares, AnaEjtehadifar, MostafaCarvalho, Ana SofiaHall, Michael JamesMorello, JuditBeck, Hans ChristianRamalho, Jose SilvaMatthiesen, RunePereira, PauloiNOVA4Health - pólo NMSNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)ElsevierHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2589-0042URNIsPartOfPURE: 149009524URNIsPartOfPURE UUID: 7155322f-e4d0-42b3-a214-8829809014b7URNIsPartOfScopus: 105024657152URNIsPartOfORCID: /0000-0002-9908-2290/work/201632881URNIsPartOfPubMed: 41503212URNIsPartOfWOS: 001642956100001DOIIsPartOf10.1016/j.isci.2025.1143052026-01-14T15:55:17Z2026-01-162026-01-16T00:00:00ZHandlehttp://hdl.handle.net/10362/199059http://purl.org/coar/access_right/c_abf2open accessCell biologyMolecular biologyGeneral17755381 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/09691016-82be-463c-8a75-a4f097a50b99/download |
| spellingShingle | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis Ferreira, Joao Vasco Cell biology Molecular biology General |
| status | SINGLETON |
| subject.fl_str_mv | Cell biology Molecular biology General |
| title | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| title_full | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| title_fullStr | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| title_full_unstemmed | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| title_short | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| title_sort | LAMP2A regulates endosomal protein composition and membrane identity in exosome biogenesis |
| topic | Cell biology Molecular biology General |
| topic_facet | Cell biology Molecular biology General |
| url | http://hdl.handle.net/10362/199059 |
| visible | 1 |