| First Author | Cong Q | Year | 2020 |
| Journal | Nat Neurosci | Volume | 23 |
| Issue | 9 | Pages | 1067-1078 |
| PubMed ID | 32661396 | Mgi Jnum | J:298253 |
| Mgi Id | MGI:6478742 | Doi | 10.1038/s41593-020-0672-0 |
| Citation | Cong Q, et al. (2020) The endogenous neuronal complement inhibitor SRPX2 protects against complement-mediated synapse elimination during development. Nat Neurosci 23(9):1067-1078 |
| abstractText | Complement-mediated synapse elimination has emerged as an important process in both brain development and neurological diseases, but whether neurons express complement inhibitors that protect synapses against complement-mediated synapse elimination remains unknown. Here, we show that the sushi domain protein SRPX2 is a neuronally expressed complement inhibitor that regulates complement-dependent synapse elimination. SRPX2 directly binds to C1q and blocks its activity, and SRPX2(-/Y) mice show increased C3 deposition and microglial synapse engulfment. They also show a transient decrease in synapse numbers and increase in retinogeniculate axon segregation in the lateral geniculate nucleus. In the somatosensory cortex, SRPX2(-/Y) mice show decreased thalamocortical synapse numbers and increased spine pruning. C3(-/-);SRPX2(-/Y) double-knockout mice exhibit phenotypes associated with C3(-/-) mice rather than SRPX2(-/Y) mice, which indicates that C3 is necessary for the effect of SRPX2 on synapse elimination. Together, these results show that SRPX2 protects synapses against complement-mediated elimination in both the thalamus and the cortex. |
