| Literature DB >> 32661396 |
Qifei Cong1, Breeanne M Soteros1, Mackenna Wollet2, Jun Hee Kim2, Gek-Ming Sia3.
Abstract
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.Entities:
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Year: 2020 PMID： 32661396 PMCID： PMC7483802 DOI： 10.1038/s41593-020-0672-0
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884