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 Bae, Jaewon Ko and Eunjoon Kim ()
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Eunkyung Lie: Korea Advanced Institute for Science and Technology
Ji Seung Ko: College of Life Science and Biotechnology, Yonsei University
Su-Yeon Choi: Center for Synaptic Brain Dysfunctions, Institute for Basic Science
Junyeop Daniel Roh: Center for Synaptic Brain Dysfunctions, Institute for Basic Science
Yi Sul Cho: School of Dentistry, Kyungpook National University
Ran Noh: Center for Cognition and Sociality, Institute for Basic Science
Doyoun Kim: Center for Synaptic Brain Dysfunctions, Institute for Basic Science
Yan Li: Center for Synaptic Brain Dysfunctions, Institute for Basic Science
Hyeyeon Kang: Yonsei University College of Medicine
Tae-Yong Choi: Seoul National University School of Dentistry
Jungyong Nam: Korea Advanced Institute for Science and Technology
Won Mah: School of Dentistry, Kyungpook National University
Dongmin Lee: Biomedical Science, College of Medicine, Korea University
Seong-Gyu Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute for Science and Technology
Ho Min Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute for Science and Technology
Hyun Kim: Biomedical Science, College of Medicine, Korea University
Se-Young Choi: Seoul National University School of Dentistry
Ji Won Um: Yonsei University College of Medicine
Myoung-Goo Kang: Center for Cognition and Sociality, Institute for Basic Science
Yong Chul Bae: School of Dentistry, Kyungpook National University
Jaewon Ko: College of Life Science and Biotechnology, Yonsei University
Eunjoon Kim: Korea Advanced Institute for Science and Technology

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12328

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