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 n

SUBMITTER: Cong Q 

PROVIDER: S-EPMC7483802 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature