| First Author | Zhang P | Year | 2018 |
| Journal | Cell | Volume | 174 |
| Issue | 6 | Pages | 1450-1464.e23 |
| PubMed ID | 30100184 | Mgi Jnum | J:277096 |
| Mgi Id | MGI:6284900 | Doi | 10.1016/j.cell.2018.07.002 |
| Citation | Zhang P, et al. (2018) Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships. Cell 174(6):1450-1464.e23 |
| abstractText | Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin's role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced survival, as well as structural and functional deficits at central synapses. HS directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual binding mode involving intrinsic glycan and protein domains for canonical synapse-organizing complexes. Neurexin HS chains also bind novel ligands, potentially expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS structure is heterogeneous, our findings indicate an additional dimension to neurexin diversity, provide a molecular basis for fine-tuning synaptic function, and open therapeutic directions targeting glycan-binding motifs critical for brain development. |
