期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 10, 页码 4057-4062出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1209881110
关键词
leucine-rich repeat; neuropsychiatic disorder; synaptic cell-adhesion
资金
- National Research Foundation of Korea [2011-0028337, 2012-0000808]
- International Human Frontier Science Program Organization [LT00021/2008-L]
- Yonsei University
- POSCO TJ Park Foundation
- Institute for Basic Science (E.K.)
- National Research Foundation of Korea [2011-0028337] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 sigma (PTP sigma), in particular, was specifically required for excitatory synaptic differentiation by Slitrks, whereas PTP delta 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.
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