All Publications

  • Post-transcriptional modular synthetic receptors. Nature chemical biology Zhang, X., Mille-Fragoso, L. S., Kaseniit, K. E., Lee, A. P., Zhang, M., Call, C. C., Hu, Y., Xie, Y., Gao, X. J. 2025

    Abstract

    Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization-Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by adenosine deaminases acting on RNA. LIDAR is compatible with various receptor architectures in different cellular contexts and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Lastly, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.

    View details for DOI 10.1038/s41589-025-01872-w

    View details for PubMedID 40155716

    View details for PubMedCentralID 9041813

  • Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching. Cell Xu, C., Li, Z., Lyu, C., Hu, Y., McLaughlin, C. N., Wong, K. K., Xie, Q., Luginbuhl, D. J., Li, H., Udeshi, N. D., Svinkina, T., Mani, D. R., Han, S., Li, T., Li, Y., Guajardo, R., Ting, A. Y., Carr, S. A., Li, J., Luo, L. 2024

    Abstract

    In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.

    View details for DOI 10.1016/j.cell.2024.06.022

    View details for PubMedID 38996528

  • Post-Transcriptional Modular Synthetic Receptors. bioRxiv : the preprint server for biology Zhang, X., Mille-Fragoso, L. S., Kaseniit, K. E., Call, C. C., Zhang, M., Hu, Y., Xie, Y., Gao, X. J. 2024

    Abstract

    Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by ADAR. LIDAR is compatible with various receptor architectures in different cellular contexts, and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Finally, LIDAR is compatible with compact encoding and can be delivered by synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.

    View details for DOI 10.1101/2024.05.03.592453

    View details for PubMedID 38746461

    View details for PubMedCentralID PMC11092781