| First Author | Trotter JH | Year | 2019 |
| Journal | J Cell Biol | Volume | 218 |
| Issue | 8 | Pages | 2677-2698 |
| PubMed ID | 31262725 | Mgi Jnum | J:279669 |
| Mgi Id | MGI:6343142 | Doi | 10.1083/jcb.201812076 |
| Citation | Trotter JH, et al. (2019) Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters. J Cell Biol 218(8):2677-2698 |
| abstractText | Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with approximately 4-6% of neurexin-1 and approximately 2-3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40-50% to approximately 80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage. |
