Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells
The immunoglobulin-like lectin receptor CD169 (Siglec-1) mediates the capture of HIV-1 by activated dendritic cells (DCs) through binding to sialylated ligands. These interactions result in a more efficient virus capture as compared to resting DCs, although the underlying mechanisms are poorly under...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78836 |
| _version_ | 1797854798132805632 |
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| author | Enric Gutiérrez-Martínez Susana Benet Garrabé Nicolas Mateos Itziar Erkizia Jon Ander Nieto-Garai Maier Lorizate Kyra JE Borgman Carlo Manzo Felix Campelo Nuria Izquierdo-Useros Javier Martinez-Picado Maria F Garcia-Parajo |
| author_facet | Enric Gutiérrez-Martínez Susana Benet Garrabé Nicolas Mateos Itziar Erkizia Jon Ander Nieto-Garai Maier Lorizate Kyra JE Borgman Carlo Manzo Felix Campelo Nuria Izquierdo-Useros Javier Martinez-Picado Maria F Garcia-Parajo |
| author_sort | Enric Gutiérrez-Martínez |
| collection | DOAJ |
| description | The immunoglobulin-like lectin receptor CD169 (Siglec-1) mediates the capture of HIV-1 by activated dendritic cells (DCs) through binding to sialylated ligands. These interactions result in a more efficient virus capture as compared to resting DCs, although the underlying mechanisms are poorly understood. Using a combination of super-resolution microscopy, single-particle tracking and biochemical perturbations we studied the nanoscale organization of Siglec-1 on activated DCs and its impact on viral capture and its trafficking to a single viral-containing compartment. We found that activation of DCs leads to Siglec-1 basal nanoclustering at specific plasma membrane regions where receptor diffusion is constrained by Rho-ROCK activation and formin-dependent actin polymerization. Using liposomes with varying ganglioside concentrations, we further demonstrate that Siglec-1 nanoclustering enhances the receptor avidity to limiting concentrations of gangliosides carrying sialic ligands. Binding to either HIV-1 particles or ganglioside-bearing liposomes lead to enhanced Siglec-1 nanoclustering and global actin rearrangements characterized by a drop in RhoA activity, facilitating the final accumulation of viral particles in a single sac-like compartment. Overall, our work provides new insights on the role of the actin machinery of activated DCs in regulating the formation of basal Siglec-1 nanoclustering, being decisive for the capture and actin-dependent trafficking of HIV-1 into the virus-containing compartment. |
| first_indexed | 2024-04-09T20:13:06Z |
| format | Article |
| id | doaj.art-5f42cba530f24b06adcd14390473871e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T20:13:06Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5f42cba530f24b06adcd14390473871e2023-03-31T15:48:45ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.78836Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cellsEnric Gutiérrez-Martínez0Susana Benet Garrabé1Nicolas Mateos2Itziar Erkizia3Jon Ander Nieto-Garai4https://orcid.org/0000-0002-8665-099XMaier Lorizate5Kyra JE Borgman6https://orcid.org/0000-0001-7898-2911Carlo Manzo7https://orcid.org/0000-0002-8625-0996Felix Campelo8https://orcid.org/0000-0002-0786-9548Nuria Izquierdo-Useros9https://orcid.org/0000-0002-1039-1821Javier Martinez-Picado10https://orcid.org/0000-0002-4916-2129Maria F Garcia-Parajo11https://orcid.org/0000-0001-6618-3944ICFO – Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainLluita contra la sida foundation, Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, SpainICFO – Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainIrsiCaixa AIDS Research Institute, Badalona, SpainDepartment of Biochemistry and Molecular Biology, Universidad del País Vasco, Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Universidad del País Vasco, Bilbao, SpainICFO – Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainFacultat de Ciències i Tecnologia, Universitat de Vic - Universitat Central de Catalunya, Vic, SpainICFO – Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainIrsiCaixa AIDS Research Institute, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain; CIBER de enfermedades infecciosas, Madrid, SpainIrsiCaixa AIDS Research Institute, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain; CIBER de enfermedades infecciosas, Madrid, Spain; AIDS and Related Illnesses, Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic - Central University of Catalonia, Vic, Spain; ICREA, Barcelona, SpainICFO – Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain; ICREA, Barcelona, SpainThe immunoglobulin-like lectin receptor CD169 (Siglec-1) mediates the capture of HIV-1 by activated dendritic cells (DCs) through binding to sialylated ligands. These interactions result in a more efficient virus capture as compared to resting DCs, although the underlying mechanisms are poorly understood. Using a combination of super-resolution microscopy, single-particle tracking and biochemical perturbations we studied the nanoscale organization of Siglec-1 on activated DCs and its impact on viral capture and its trafficking to a single viral-containing compartment. We found that activation of DCs leads to Siglec-1 basal nanoclustering at specific plasma membrane regions where receptor diffusion is constrained by Rho-ROCK activation and formin-dependent actin polymerization. Using liposomes with varying ganglioside concentrations, we further demonstrate that Siglec-1 nanoclustering enhances the receptor avidity to limiting concentrations of gangliosides carrying sialic ligands. Binding to either HIV-1 particles or ganglioside-bearing liposomes lead to enhanced Siglec-1 nanoclustering and global actin rearrangements characterized by a drop in RhoA activity, facilitating the final accumulation of viral particles in a single sac-like compartment. Overall, our work provides new insights on the role of the actin machinery of activated DCs in regulating the formation of basal Siglec-1 nanoclustering, being decisive for the capture and actin-dependent trafficking of HIV-1 into the virus-containing compartment.https://elifesciences.org/articles/78836actin cytoskeletonreceptor nanoclusteringsuper-resolution microscopysingle-particle tracking |
| spellingShingle | Enric Gutiérrez-Martínez Susana Benet Garrabé Nicolas Mateos Itziar Erkizia Jon Ander Nieto-Garai Maier Lorizate Kyra JE Borgman Carlo Manzo Felix Campelo Nuria Izquierdo-Useros Javier Martinez-Picado Maria F Garcia-Parajo Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells eLife actin cytoskeleton receptor nanoclustering super-resolution microscopy single-particle tracking |
| title | Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells |
| title_full | Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells |
| title_fullStr | Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells |
| title_full_unstemmed | Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells |
| title_short | Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells |
| title_sort | actin regulated siglec 1 nanoclustering influences hiv 1 capture and virus containing compartment formation in dendritic cells |
| topic | actin cytoskeleton receptor nanoclustering super-resolution microscopy single-particle tracking |
| url | https://elifesciences.org/articles/78836 |
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