SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Yeonsoo Choi; Jungyong Nam; Daniel J. Whitcomb; Yoo Sung Song; Doyoun Kim; Sangmin Jeon; Ji Won Um; Seong Gyu Lee; Jooyeon Woo; Seok Kyu Kwon; Yan Li; Won Mah; Ho Min Kim; Jaewon Ko; Kwangwook Cho; Eunjoon Kim

doi:10.1038/srep26676

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Yeonsoo Choi
, Jungyong Nam
, Daniel J. Whitcomb
, Yoo Sung Song
, Doyoun Kim
, Sangmin Jeon
, Ji Won Um
, Seong Gyu Lee
, Jooyeon Woo
, Seok Kyu Kwon
, Yan Li
, Won Mah
, Ho Min Kim
, Jaewon Ko
, Kwangwook Cho
, Eunjoon Kim

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.

Original language	English
Article number	26676
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep26676
State	Published - 26 May 2016

Bibliographical note

Funding Information:
This work was supported by the MRC-Wellcome Trust Neurodegenerative Diseases Initiative (to K.C.), the Wolfson Research Merit Award and Royal Society London (to K.C.), the Yonsei University Future-leading Research Initiative of 2014 (to J.K.), the National Research Foundation funded by the Ministry of Education, Science and Technology (NRF-2013R1A6A3A04061338 to J.W.U.), and Global Postdoctoral Fellowship funded by National Research Foundation of Korea (2013-034548 to Y.C.), the Institute for Basic Science (IBS) (IBSR002-D1 to E.K.).

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@article{52902f35214d4231b8ca45dd31948a88,

title = "SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development",

abstract = "Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.",

author = "Yeonsoo Choi and Jungyong Nam and Whitcomb, \{Daniel J.\} and Song, \{Yoo Sung\} and Doyoun Kim and Sangmin Jeon and Um, \{Ji Won\} and Lee, \{Seong Gyu\} and Jooyeon Woo and Kwon, \{Seok Kyu\} and Yan Li and Won Mah and Kim, \{Ho Min\} and Jaewon Ko and Kwangwook Cho and Eunjoon Kim",

note = "Funding Information: This work was supported by the MRC-Wellcome Trust Neurodegenerative Diseases Initiative (to K.C.), the Wolfson Research Merit Award and Royal Society London (to K.C.), the Yonsei University Future-leading Research Initiative of 2014 (to J.K.), the National Research Foundation funded by the Ministry of Education, Science and Technology (NRF-2013R1A6A3A04061338 to J.W.U.), and Global Postdoctoral Fellowship funded by National Research Foundation of Korea (2013-034548 to Y.C.), the Institute for Basic Science (IBS) (IBSR002-D1 to E.K.).",

year = "2016",

month = may,

day = "26",

doi = "10.1038/srep26676",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

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T1 - SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

AU - Choi, Yeonsoo

AU - Nam, Jungyong

AU - Whitcomb, Daniel J.

AU - Song, Yoo Sung

AU - Kim, Doyoun

AU - Jeon, Sangmin

AU - Um, Ji Won

AU - Lee, Seong Gyu

AU - Woo, Jooyeon

AU - Kwon, Seok Kyu

AU - Li, Yan

AU - Mah, Won

AU - Kim, Ho Min

AU - Ko, Jaewon

AU - Cho, Kwangwook

AU - Kim, Eunjoon

N1 - Funding Information: This work was supported by the MRC-Wellcome Trust Neurodegenerative Diseases Initiative (to K.C.), the Wolfson Research Merit Award and Royal Society London (to K.C.), the Yonsei University Future-leading Research Initiative of 2014 (to J.K.), the National Research Foundation funded by the Ministry of Education, Science and Technology (NRF-2013R1A6A3A04061338 to J.W.U.), and Global Postdoctoral Fellowship funded by National Research Foundation of Korea (2013-034548 to Y.C.), the Institute for Basic Science (IBS) (IBSR002-D1 to E.K.).

PY - 2016/5/26

Y1 - 2016/5/26

N2 - Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.

AB - Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.

UR - https://www.scopus.com/pages/publications/84971254351

U2 - 10.1038/srep26676

DO - 10.1038/srep26676

M3 - Article

C2 - 27225731

AN - SCOPUS:84971254351

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 26676

ER -

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Abstract

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