SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion
Authors
Eunkyung Lie ; Ji Seung Ko ; Su-Yeon Choi ; Junyeop Daniel Roh ; Yi Sul Cho ; Ran Noh ; Doyoun Kim ; Yan Li ; Hyeyeon Kang ; Tae-Yong Choi ; Jungyong Nam ; Won Mah ; Dongmin Lee ; Seong-Gyu Lee ; Ho Min Kim ; Hyun Kim ; Se-Young Choi ; Ji Won Um ; Myoung-Goo Kang ; Yong Chul Bae ; Jaewon Ko ; Eunjoon Kim
Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.