ArticleCellular and molecular life sciences : CMLS2013
Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation impairs MTOC docking, immune synapse formation and T cell activation.
Article in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Cytoskeleton Remodeling-Related Proteins Represent a Specific Salivary Signature in PSC Patients.Molecules (Basel, Switzerland) · 2024Article
- Generation of Photocaged Nanobodies for Intracellular Applications in an Animal Using Genetic Code Expansion and Computationally Guided Protein Engineering.Chembiochem : a European journal of chemical biology · 2022Article
- L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.Cell reports · 2022Article
- Efficient T Cell Migration and Activation Require L-Plastin.Frontiers in immunology · 2022Review
- Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules.International journal of molecular sciences · 2021Article
- A comprehensive comparison between camelid nanobodies and single chain variable fragments.Biomarker research · 2021Review
- Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- LFA-1 cluster formation in T-cells depends on L-plastin phosphorylation regulated by P90Cellular and molecular life sciences : CMLS · 2021Article
- L-plastin Ser5 phosphorylation is modulated by the PI3K/SGK pathway and promotes breast cancer cell invasiveness.Cell communication and signaling : CCS · 2021Article
- Nanobodies Right in the Middle: Intrabodies as Toolbox to Visualize and Modulate Antigens in the Living Cell.Biomolecules · 2020Review
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
- Nanobody-Based Probes for Subcellular Protein Identification and Visualization.Frontiers in cellular neuroscience · 2020Review
- Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics.Frontiers in oncology · 2020Review
- Advances in targeted degradation of endogenous proteins.Cellular and molecular life sciences : CMLS · 2019Review
- Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.Angewandte Chemie (International ed. in English) · 2018Review
- Single domain antibodies for the knockdown of cytosolic and nuclear proteins.Protein science : a publication of the Protein Society · 2017Review
- Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia.The Journal of biological chemistry · 2016Article
- Nanobodies as Probes for Protein Dynamics in Vitro and in Cells.The Journal of biological chemistry · 2016Review
- A nanobody modulates the p53 transcriptional program without perturbing its functional architecture.Nucleic acids research · 2014Article
- Chaperone nanobodies protect gelsolin against MT1-MMP degradation and alleviate amyloid burden in the gelsolin amyloidosis mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The T cell integrin receptor LFA-1 orchestrates adhesion between T cells and antigen-presenting cells (APCs), resulting in formation of a contact zone known as the immune synapse (IS) which is supported by the cytoskeleton. L-plastin is a leukocyte-specific actin bundling protein that rapidly redistributes to the immune synapse following T cell-APC engagement. We used single domain antibodies (nanobodies, derived from camelid heavy-chain only antibodies) directed against functional and structural modules of L-plastin to investigate its contribution to formation of an immune synapse between Raji cells and human peripheral blood mononuclear cells or Jurkat T cells. Nanobodies that interact either with the EF hands or the actin binding domains of L-plastin both trapped L-plastin in an inactive conformation, causing perturbation of IS formation, MTOC docking towards the plasma membrane, T cell proliferation and IL-2 secretion. Both nanobodies delayed Ser(5) phosphorylation of L-plastin which is required for enhanced bundling activity. Moreover, one nanobody delayed LFA-1 phosphorylation, reduced the association between LFA-1 and L-plastin and prevented LFA-1 enrichment at the IS. Our findings reveal subtle mechanistic details that are difficult to attain by conventional means and show that L-plastin contributes to immune synapse formation at distinct echelons.
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