SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion

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 BaeJaewon Ko, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish
Article number12328
JournalNature Communications
Volume7
DOIs
StatePublished - 2 Aug 2016

Bibliographical note

Publisher Copyright:
© The Author(s) 2016.

Fingerprint

Dive into the research topics of 'SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion'. Together they form a unique fingerprint.

Cite this