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

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Title
Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases
Author(s)
Yeong Shin Yim; Younghee Kwon; Jungyong Nam; Hong In Yoon; Kangduk Lee; Dong Goo Kim; Eun Joon Kim; Chul Hoon Kim; Jaewon Ko
Subject
leucine-rich repeat | neuropsychiatic disorder | synaptic cell-adhesion
Publication Date
2013-03
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.110, no.10, pp.4057 - 4062
Publisher
NATL ACAD SCIENCES
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.
URI
https://pr.ibs.re.kr/handle/8788114/1364
DOI
10.1073/pnas.1209881110
ISSN
0027-8424
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
2013-03-05-PNAS-Slitrks control excitatory.pdfDownload

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