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

被引：28

作者：

Lie, Eunkyung ^{[1
]}

Ko, Ji Seung ^{[2
]}

Choi, Su-Yeon ^{[3
]}

Roh, Junyeop Daniel ^{[3
]}

Cho, Yi Sul ^{[4
]}

Noh, Ran ^{[5
]}

Kim, Doyoun ^{[3
]}

Li, Yan ^{[3
]}

Kang, Hyeyeon ^{[6
,7
]}

Choi, Tae-Yong ^{[8
]}

Nam, Jungyong ^{[1
]}

Mah, Won ^{[4
]}

Lee, Dongmin ^{[9
,10
]}

Lee, Seong-Gyu ^{[11
]}

Kim, Ho Min ^{[11
]}

Kim, Hyun ^{[9
,10
]}

Choi, Se-Young ^{[8
]}

Um, Ji Won ^{[6
,7
]}

Kang, Myoung-Goo ^{[5
,11
]}

Bae, Yong Chul ^{[4
]}

Ko, Jaewon ^{[2
]}

Kim, Eunjoon ^{[1
,3
]}

机构：

[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 305701, South Korea

[2] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 120749, South Korea

[3] Inst for Basic Sci Korea, Ctr Synapt Brain Dysfunct, Daejeon 305701, South Korea

[4] Kyungpook Natl Univ, Sch Dent, Dept Anat & Neurobiol, Daegu 700412, South Korea

[5] Inst for Basic Sci Korea, Ctr Cognit & Social, Daejeon 305701, South Korea

[6] Yonsei Univ, Coll Med, Dept Physiol, Seoul 120752, South Korea

[7] Yonsei Univ, Coll Med, PLUS Project Med Sci BK21, Seoul 120752, South Korea

[8] Seoul Natl Univ, Sch Dent, Dept Physiol, Seoul 110749, South Korea

[9] Korea Univ, Coll Med, Dept Anat, Seoul 136705, South Korea

[10] Korea Univ, Coll Med, Div Brain Korea 21, Biomed Sci, Seoul 136705, South Korea

[11] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 305701, South Korea

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

新加坡国家研究基金会;

关键词：

AUTISM SPECTRUM DISORDERS; NMDA RECEPTOR; LAR-RPTPS; MOLECULES; NEUROLIGINS; FAMILY; NEUREXINS; PROTEINS; COMPLEXES; INTERACTS;

D O I：

10.1038/ncomms12328

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 5 条

[1] 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
Eunjoon Kim
[J]. Nature Communications, 7
[2] Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion
Li, Yan
Zhang, Peng
Choi, Tae-Yong
Park, Sook Kyung
Park, Hanwool
Lee, Eun-Jae
Lee, Dongsoo
Roh, Junyeop Daniel
Mah, Won
Kim, Ryunhee
Kim, Yangsik
Kwon, Harah
Bae, Yong Chul
Choi, Se-Young
Craig, Ann Marie
Kim, Eunjoon
[J]. CELL REPORTS, 2015, 12 (10): : 1618 - 1630
[3] Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses
Jooyeon Woo
Seok-Kyu Kwon
Seungwon Choi
Seho Kim
Jae-Ran Lee
Anthone W Dunah
Morgan Sheng
Eunjoon Kim
[J]. Nature Neuroscience, 2009, 12 : 428 - 437
[4] Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses
Woo, Jooyeon
Kwon, Seok-Kyu
Choi, Seungwon
Kim, Seho
Lee, Jae-Ran
Dunah, Anthone W.
Sheng, Morgan
Kim, Eunjoon
[J]. NATURE NEUROSCIENCE, 2009, 12 (04) : 428 - 437
[5] Trans-synaptic Adhesions between Netrin-G Ligand-3 (NGL-3) and Receptor Tyrosine Phosphatases LAR, Protein-tyrosine Phosphatase δ (PTPδ), and PTPσ via Specific Domains Regulate Excitatory Synapse Formation
Kwon, Seok-Kyu
Woo, Jooyeon
Kim, Soo-Young
Kim, Hyun
Kim, Eunjoon
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (18) : 13966 - 13978

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