한빛사논문, 상위피인용논문
Yeong Shin Yima,1, Younghee Kwonb,1, Jungyong Namc, Hong In Yoona, Kangduk Leeb, Dong Goo Kima, Eunjoon Kimc, Chul Hoon Kima,2, and Jaewon Kob,2
aDepartment of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;
bDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea; and
cCenter for Synaptic Brain Dysfunctions, Institute for Basic Science, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
Edited by Thomas C. Sudhof, Stanford University School of Medicine, Stanford, CA, and approved December 26, 2012 (received for review June 11, 2012)
Footnotes
1Y.S.Y. and Y.K. contributed equally to this study.
2To whom correspondence may be addressed.
Author contributions: E.K., C.H.K., and J.K. designed research; Y.S.Y., Y.K., J.N., H.I.Y., and J.K. performed research; K.L. and J.K. contributed new reagents/analytic tools; Y.S.Y., J.N., D.G.K., C.H.K., and J.K. analyzed data; and J.K. wrote the paper.
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.
leucine-rich repeat, neuropsychiatic disorder, synaptic cell-adhesion
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