Fredrik H Sterky, Justin H Trotter, Sung-Jin Lee, Christian V Recktenwald, Xiao Du, Bo Zhou, Peng Zhou, Jochen Schwenk, Bernd Fakler, Thomas C Südhof
Proceedings of the National Academy of Sciences of the United States of America 2017 Feb 14Establishment, specification, and validation of synaptic connections are thought to be mediated by interactions between pre- and postsynaptic cell-adhesion molecules. Arguably, the best-characterized transsynaptic interactions are formed by presynaptic neurexins, which bind to diverse postsynaptic ligands. In a proteomic screen of neurexin-1 (Nrxn1) complexes immunoisolated from mouse brain, we identified carbonic anhydrase-related proteins CA10 and CA11, two homologous, secreted glycoproteins of unknown function that are predominantly expressed in brain. We found that CA10 directly binds in a cis configuration to a conserved membrane-proximal, extracellular sequence of α- and β-neurexins. The CA10-neurexin complex is stable and stoichiometric, and results in formation of intermolecular disulfide bonds between conserved cysteine residues in neurexins and CA10. CA10 promotes surface expression of α- and β-neurexins, suggesting that CA10 may form a complex with neurexins in the secretory pathway that facilitates surface transport of neurexins. Moreover, we observed that the Nrxn1 gene expresses from an internal 3' promoter a third isoform, Nrxn1γ, that lacks all Nrxn1 extracellular domains except for the membrane-proximal sequences and that also tightly binds to CA10. Our data expand the understanding of neurexin-based transsynaptic interaction networks by providing further insight into the interactions nucleated by neurexins at the synapse.
Fredrik H Sterky, Justin H Trotter, Sung-Jin Lee, Christian V Recktenwald, Xiao Du, Bo Zhou, Peng Zhou, Jochen Schwenk, Bernd Fakler, Thomas C Südhof. Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand. Proceedings of the National Academy of Sciences of the United States of America. 2017 Feb 14;114(7):E1253-E1262
PMID: 28154140
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