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Publication : Molecular self-avoidance in synaptic neurexin complexes.

First Author  Wang CY Year  2021
Journal  Sci Adv Volume  7
Issue  51 Pages  eabk1924
PubMed ID  34919427 Mgi Jnum  J:317210
Mgi Id  MGI:6842839 Doi  10.1126/sciadv.abk1924
Citation  Wang CY, et al. (2021) Molecular self-avoidance in synaptic neurexin complexes. Sci Adv 7(51):eabk1924
abstractText  Synapses are thought to be organized by interactions of presynaptic neurexins with postsynaptic ligands, particularly with neuroligins and cerebellins. However, when a neuron forms adjacent pre- and postsynaptic specializations, as in dendrodendritic or axo-axonic synapses, nonfunctional cis neurexin/ligand interactions would be energetically favored. Here, we reveal an organizational principle for preventing synaptic cis interactions ("self-avoidance"). Using dendrodendritic synapses between mitral and granule cells in the olfactory bulb as a paradigm, we show that, owing to its higher binding affinity, cerebellin-1 blocks the cis interaction of neurexins with neuroligins, thereby enabling trans neurexin/neuroligin interaction. In mitral cells, ablating either cerebellin-1 or neuroligins severely impaired granule cellmitral cell synapses, as did overexpression of wild-type neurexins but not of mutant neurexins unable to bind to neuroligins. Our data uncover a molecular interaction network that organizes the self-avoidance of nonfunctional neurexin/ligand cis interactions, thus allowing assembly of physiological trans interactions.
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