| First Author | Boudkkazi S | Year | 2023 |
| Journal | Neuron | Volume | 111 |
| Issue | 16 | Pages | 2544-2556.e9 |
| PubMed ID | 37591201 | Mgi Jnum | J:341089 |
| Mgi Id | MGI:7521890 | Doi | 10.1016/j.neuron.2023.07.013 |
| Citation | Boudkkazi S, et al. (2023) A Noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors. Neuron 111(16):2544-2556.e9 |
| abstractText | Information processing and storage in the brain rely on AMPA-receptors (AMPARs) and their context-dependent dynamics in synapses and extra-synaptic sites. We found that distribution and dynamics of AMPARs in the plasma membrane are controlled by Noelins, a three-member family of conserved secreted proteins expressed throughout the brain in a cell-type-specific manner. Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration with a variety of secreted and membrane-anchored proteins including Neurexin1, Neuritin1, and Seizure 6-like. Knock out of Noelins1-3 profoundly reduced AMPARs in synapses onto excitatory and inhibitory (inter)neurons, decreased their density and clustering in dendrites, and abolished activity-dependent synaptic plasticity. Our results uncover an endogenous mechanism for extracellular anchoring of AMPARs and establish Noelin-organized networks as versatile determinants of constitutive and context-dependent neurotransmission. |
