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Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

Authors
 Yeong Shin Yim  ;  Younghee Kwon  ;  Jungyong Nam  ;  Hong In Yoon  ;  Kangduk Lee  ;  Dong Goo Kim  ;  Eunjoon Kim  ;  Chul Hoon Kim  ;  Jaewon Ko 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.110(10) : 4057-4062, 2013 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2013
MeSH
Animals ; Base Sequence ; Brain/physiology ; Cells, Cultured ; Gene Knockdown Techniques ; Hippocampus/cytology ; Hippocampus/physiology ; Nerve Tissue Proteins/antagonists & inhibitors ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/physiology* ; RNA, Small Interfering/genetics ; Rats ; Receptor-Like Protein Tyrosine Phosphatases, Class 2/physiology* ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Synapses/physiology* ; Up-Regulation
Keywords
leucine-rich repeat ; neuropsychiatic disorder ; synaptic cell-adhesion
Abstract
The balance between excitatory and inhibitory synaptic inputs, which is governed by multiple synapse organizers, controls neural circuit functions and behaviors. Slit- and Trk-like proteins (Slitrks) are a family of synapse organizers, whose emerging synaptic roles are incompletely understood. Here, we report that Slitrks are enriched in postsynaptic densities in rat brains. Overexpression of Slitrks promoted synapse formation, whereas RNAi-mediated knockdown of Slitrks decreased synapse density. Intriguingly, Slitrks were required for both excitatory and inhibitory synapse formation in an isoform-dependent manner. Moreover, Slitrks required distinct members of the leukocyte antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family to trigger synapse formation. Protein tyrosine phosphatase σ (PTPσ), in particular, was specifically required for excitatory synaptic differentiation by Slitrks, whereas PTPδ was necessary for inhibitory synapse differentiation. Taken together, these data suggest that combinatorial interactions of Slitrks with LAR-RPTP family members maintain synapse formation to coordinate excitatory–inhibitory balance.
Files in This Item:
T201300447.pdf Download
DOI
10.1073/pnas.1209881110
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Yim, Yeong Shin(임영신)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86425
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