Print Email Facebook Twitter Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition Title Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition Author Gogou, C. (TU Delft BN/Dimphna Meijer Lab) Beugelink, J. Wouter (Universiteit Utrecht) Pereira Frias, C.S. (TU Delft BN/Dimphna Meijer Lab) Kresik, L.K. (TU Delft BN/Dimphna Meijer Lab) Jaroszynska, Natalia (King’s College London) Drescher, Uwe (King’s College London) Janssen, Bert J.C. (Universiteit Utrecht) Hindges, Robert (King’s College London) Meijer, D.H.M. (TU Delft BN/Dimphna Meijer Lab) Date 2024 Abstract Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules at the cell surface. Alternative splicing of cell adhesion molecules provides additional specificity in forming neuronal connections. For the teneurin family of cell adhesion molecules, alternative splicing of the EGF-repeats and NHL domain controls synaptic protein-protein interactions. Here we present cryo-EM structures of the compact dimeric ectodomain of two teneurin-3 isoforms that harbour the splice insert in the EGF-repeats. This dimer is stabilised by an EGF8-ABD contact between subunits. Cryo-EM reconstructions of all four splice variants, together with SAXS and negative stain EM, reveal compacted dimers for each, with variant-specific dimeric arrangements. This results in specific trans-cellular interactions, as tested in cell clustering and stripe assays. The compact conformations provide a structural basis for teneurin homo- and heterophilic interactions. Altogether, our findings demonstrate how alternative splicing results in rearrangements of the dimeric subunits, influencing neuronal recognition and likely circuit wiring. Subject OA-Fund TU Delft To reference this document use: http://resolver.tudelft.nl/uuid:b2b71071-298f-4c51-bb5f-14238c7c6dbd DOI https://doi.org/10.1038/s41467-024-47763-x ISSN 2041-1723 Source Nature Communications, 15 (1) Part of collection Institutional Repository Document type journal article Rights © 2024 C. Gogou, J. Wouter Beugelink, C.S. Pereira Frias, L.K. Kresik, Natalia Jaroszynska, Uwe Drescher, Bert J.C. Janssen, Robert Hindges, D.H.M. Meijer Files PDF s41467-024-47763-x.pdf 5.78 MB Close viewer /islandora/object/uuid:b2b71071-298f-4c51-bb5f-14238c7c6dbd/datastream/OBJ/view