Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases
Yeong Shin Yim ; Younghee Kwon ; Jungyong Nam ; Hong In Yoon ; Kangduk Lee ; Dong Goo Kim ; Eunjoon Kim ; Chul Hoon Kim ; Jaewon Ko
Proceedings of the National Academy of Sciences of the United States of America, Vol.110(10) : 4057–4062, 2013
Proceedings of the National Academy of Sciences of the United States of America
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.