@article{097bff2096314ea9b95b4b3ee0fba6aa,
title = "The endogenous neuronal complement inhibitor SRPX2 protects against complement-mediated synapse elimination during development",
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.",
author = "Qifei Cong and Soteros, {Breeanne M.} and Mackenna Wollet and Kim, {Jun Hee} and Sia, {Gek Ming}",
note = "Funding Information: We thank A. Tenner (UC Irvine) for complement-related reagents. We thank D. Lodge (UTHSCA) for use of his microscope system, and D. Morilak (UTHSCSA) for use of histology equipment. We also thank M. Baum (Beth Steven{\textquoteright}s Lab, Harvard) for technical advice on eye injections. CRISPR–Cas9 pronuclear injections were performed at the Johns Hopkins Transgenic Core Laboratory, and screening of founders and subsequent work was performed at UTHSCSA. This work was funded by the NARSAD Young Investigator grant number 25248 (to G.-M.S.), the William and Ella Owens Medical Research Foundation (to G.-M.S.), the Rising STARs award from the University of Texas System (to G.-M.S.), NINDS-R01NS112389 (to G.-M.S.) and NIDCD-R01DC013157 (to J.H.K.). Images were generated at the Core Optical Imaging Facility, which is supported by UTHSCSA, NCI-P30CA54174 (CTRC at UTHSCSA) and NIA-P01AG19316. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = sep,
day = "1",
doi = "10.1038/s41593-020-0672-0",
language = "English (US)",
volume = "23",
pages = "1067--1078",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "9",
}