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 journalArticle

16 Citations (Scopus)

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
Publication statusPublished - 2016 Aug 2

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synapses
Synapses
adhesion
Adhesion
Molecules
mice
Class 2 Receptor-Like Protein Tyrosine Phosphatases
Phosphoric Monoester Hydrolases
Plasticity
hippocampus
deletion
phosphatases
tyrosine
interactions
plastic properties
molecules
Hippocampus
Proteins
proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion. / Lie, Eunkyung; Ko, Ji Seung; Choi, Su Yeon; Roh, Junyeop Daniel; Cho, Yi Sul; Noh, Ran; Kim, Doyoun; Li, Yan; Kang, Hyeyeon; Choi, Tae Yong; Nam, Jungyong; Mah, Won; Lee, Dongmin; Lee, Seong Gyu; Kim, Ho Min; Kim, Hyun; Choi, Se Young; Um, Ji Won; Kang, Myoung Goo; Bae, Yong Chul; Ko, Jaewon; Kim, Eunjoon.

In: Nature Communications, Vol. 7, 12328, 02.08.2016.

Research output: Contribution to journalArticle

Lie, E, Ko, JS, Choi, SY, Roh, JD, Cho, YS, Noh, R, Kim, D, Li, Y, Kang, H, Choi, TY, Nam, J, Mah, W, Lee, D, Lee, SG, Kim, HM, Kim, H, Choi, SY, Um, JW, Kang, MG, Bae, YC, Ko, J & Kim, E 2016, 'SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion', Nature Communications, vol. 7, 12328. https://doi.org/10.1038/ncomms12328
Lie, Eunkyung ; Ko, Ji Seung ; Choi, Su Yeon ; Roh, Junyeop Daniel ; Cho, Yi Sul ; Noh, Ran ; Kim, Doyoun ; Li, Yan ; Kang, Hyeyeon ; Choi, Tae Yong ; Nam, Jungyong ; Mah, Won ; Lee, Dongmin ; Lee, Seong Gyu ; Kim, Ho Min ; Kim, Hyun ; Choi, Se Young ; Um, Ji Won ; Kang, Myoung Goo ; Bae, Yong Chul ; Ko, Jaewon ; Kim, Eunjoon. / SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion. In: Nature Communications. 2016 ; Vol. 7.
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