| First Author | Irala D | Year | 2024 |
| Journal | Neuron | Volume | 112 |
| Issue | 10 | Pages | 1657-1675.e10 |
| PubMed ID | 38574730 | Mgi Jnum | J:348404 |
| Mgi Id | MGI:7641214 | Doi | 10.1016/j.neuron.2024.03.007 |
| Citation | Irala D, et al. (2024) Astrocyte-secreted neurocan controls inhibitory synapse formation and function. Neuron 112(10):1657-1675.e10 |
| abstractText | Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an astrocyte-secreted inhibitory synaptogenic protein. After secretion from astrocytes, neurocan is cleaved into N- and C-terminal fragments. We found that these fragments have distinct localizations in the extracellular matrix. The neurocan C-terminal fragment localizes to synapses and controls cortical inhibitory synapse formation and function. Neurocan knockout mice lacking the whole protein or only its C-terminal synaptogenic domain have reduced inhibitory synapse numbers and function. Through super-resolution microscopy, in vivo proximity labeling by secreted TurboID, and astrocyte-specific rescue approaches, we discovered that the synaptogenic domain of neurocan localizes to somatostatin-positive inhibitory synapses and strongly regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific inhibitory synapse development in the mammalian brain. |
