ArticleScience advances2020
mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Phantom of the immunologic opera: Unmasking the role of innate lymphoid cells (ILC) in inborn errors of immunity (IEI).Journal of human immunity · 2025Review
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.Journal of clinical immunology · 2024Article
- Immune dysregulation due to bi-allelic mutation of the actin remodeling protein DIAPH1.Frontiers in immunology · 2024Article
- FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms.Frontiers in immunology · 2024Article
- mDia formins form hetero-oligomers and cooperatively maintain murine hematopoiesis.PLoS genetics · 2023Article
- Investigating Mammalian Formins with SMIFH2 Fifteen Years in: Novel Targets and Unexpected Biology.International journal of molecular sciences · 2023Review
- LPA suppresses T cell function by altering the cytoskeleton and disrupting immune synapse formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.Frontiers in cell and developmental biology · 2021Review
- Wiskott-Aldrich Syndrome Protein: Roles in Signal Transduction in T Cells.Frontiers in cell and developmental biology · 2021Review
- Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The mechanism by which the cytosolic protein Zap70 physically interacts with and phosphorylates its substrate, the transmembrane protein LAT, upon T cell receptor (TCR) stimulation remains largely obscure. In this study, we found that the pharmacological inhibition of formins, a major class of actin nucleators, suppressed LAT phosphorylation by Zap70, despite TCR stimulation-dependent phosphorylation of Zap70 remaining intact. High-resolution imaging and three-dimensional image reconstruction revealed that localization of phosphorylated Zap70 to the immune synapse (IS) and subsequent LAT phosphorylation are critically dependent on formin-mediated actin polymerization. Using knockout mice, we identify mDia1 and mDia3, which are highly expressed in T cells and which localize to the IS upon TCR activation, as the critical formins mediating this process. Our findings therefore describe previously unsuspected roles for mDia1 and mDia3 in the spatiotemporal control of Zap70-dependent LAT phosphorylation at the IS through regulation of filamentous actin, and underscore their physiological importance in TCR signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.