HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.

Detalhes bibliográficos
Autor(a) principal: Silva, Joana G.
Data de Publicação: 2016
Outros Autores: Martins, Nuno, Henriques, Ricardo, Soares, Helena
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/152375
Resumo: Funding: We thank Nuno Moreno for contributing to setting up the superresolution microscope, Claúdia Campos and Vasco Barreto for help in cloning, and Claúdia Bispo for help in intracellular calcium assay. We thank the National Institutes of Health AIDS Reagent Program for providing the HIV-1 NL4.3 and HIV-1 NL4.3 DNef constructs, the Ab against Gag, and the human IL-2.
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spelling HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.SDG 3 - Good Health and Well-beingFunding: We thank Nuno Moreno for contributing to setting up the superresolution microscope, Claúdia Campos and Vasco Barreto for help in cloning, and Claúdia Bispo for help in intracellular calcium assay. We thank the National Institutes of Health AIDS Reagent Program for providing the HIV-1 NL4.3 and HIV-1 NL4.3 DNef constructs, the Ab against Gag, and the human IL-2.The ability of HIV-1 to replicate and to establish long-term reservoirs is strongly influenced by T cell activation. Through the use of membrane-tethered, genetically encoded calcium (Ca2+) indicators, we were able to detect for the first time, to our knowledge, the formation of Ca2+ territories and determine their role in coordinating the functional signaling nanostructure of the synaptic membrane. Consequently, we report a previously unknown immune subversion mechanism involving HIV-1 exploitation, through its Nef accessory protein, of the interconnectivity among three evolutionarily conserved cellular processes: vesicle traffic, signaling compartmentalization, and the second messenger Ca2+ We found that HIV-1 Nef specifically associates with the traffic regulators MAL and Rab11b compelling the vesicular accumulation of Lck. Through its association with MAL and Rab11b, Nef co-opts Lck switchlike function driving the formation Ca2+ membrane territories, which, in turn, control the fusion of LAT-transporting Rab27 and Rab37 vesicles and the formation of LAT nanoclusters at the immunological synapse. Consequently, HIV-1 Nef disengages TCR triggering from the generation of p-LAT and p-SLP nanoclusters driving TCR signal amplification and diversification. Altogether our results indicate that HIV-1 exploits the interconnectivity among vesicle traffic, Ca2+ membrane territories, and signaling nanoclusters to modulate T cell signaling and function.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNSilva, Joana G.Martins, NunoHenriques, RicardoSoares, Helena2023-05-03T22:06:48Z2016-10-192016-10-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://hdl.handle.net/10362/152375eng1550-6606PURE: 1972213https://doi.org/10.4049/jimmunol.1601132info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:34:43Zoai:run.unl.pt:10362/152375Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:53.662352Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
title HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
spellingShingle HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
Silva, Joana G.
SDG 3 - Good Health and Well-being
title_short HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
title_full HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
title_fullStr HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
title_full_unstemmed HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
title_sort HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.
author Silva, Joana G.
author_facet Silva, Joana G.
Martins, Nuno
Henriques, Ricardo
Soares, Helena
author_role author
author2 Martins, Nuno
Henriques, Ricardo
Soares, Helena
author2_role author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Silva, Joana G.
Martins, Nuno
Henriques, Ricardo
Soares, Helena
dc.subject.por.fl_str_mv SDG 3 - Good Health and Well-being
topic SDG 3 - Good Health and Well-being
description Funding: We thank Nuno Moreno for contributing to setting up the superresolution microscope, Claúdia Campos and Vasco Barreto for help in cloning, and Claúdia Bispo for help in intracellular calcium assay. We thank the National Institutes of Health AIDS Reagent Program for providing the HIV-1 NL4.3 and HIV-1 NL4.3 DNef constructs, the Ab against Gag, and the human IL-2.
publishDate 2016
dc.date.none.fl_str_mv 2016-10-19
2016-10-19T00:00:00Z
2023-05-03T22:06:48Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/152375
url http://hdl.handle.net/10362/152375
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1550-6606
PURE: 1972213
https://doi.org/10.4049/jimmunol.1601132
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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