ArticleCell reports2021
Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Nanoscale protein clustering modulates the input-output response of cellular signalling pathways.Scientific reports · 2026Article
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Robust calibration and quantification of FRET signals using multiplexed biosensor barcoding.iScience · 2025Article
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Optogenetic control of T cells for immunomodulation.Essays in biochemistry · 2025Review
- Large-scale control over collective cell migration using light-activated epidermal growth factor receptors.Cell systems · 2025Article
- Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations.Military Medical Research · 2024Review
- Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag.Nature communications · 2024Article
- The ubiquitous nanocluster: A molecular scale organizing principle that governs cellular information flow.Current opinion in cell biology · 2024Review
- Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag.bioRxiv : the preprint server for biology · 2024Article
- Optogenetic clustering and membrane translocation of the BcLOV4 photoreceptor.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Kinase regulation by liquid-liquid phase separation.Trends in cell biology · 2023Review
- Optical sensing and control of T cell signaling pathways.Frontiers in physiology · 2023Review
- Programming cell-surface signaling by phase-separation-controlled compartmentalization.Nature chemical biology · 2022Article
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein clustering is pervasive in cell signaling, yet how signaling from higher-order assemblies differs from simpler forms of molecular organization is still poorly understood. We present an optogenetic approach to switch between oligomers and heterodimers with a single point mutation. We apply this system to study signaling from the kinase Zap70 and its substrate linker for activation of T cells (LAT), proteins that normally form membrane-localized condensates during T cell activation. We find that fibroblasts expressing synthetic Zap70:LAT clusters activate downstream signaling, whereas one-to-one heterodimers do not. We provide evidence that clusters harbor a positive feedback loop among Zap70, LAT, and Src-family kinases that binds phosphorylated LAT and further activates Zap70. Finally, we extend our optogenetic approach to the native T cell signaling context, where light-induced LAT clustering is sufficient to drive a calcium response. Our study reveals a specific signaling function for protein clusters and identifies a biochemical circuit that robustly senses protein oligomerization state.
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