Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases.
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.
Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Yeong Shin
YS
Yim
Younghee
Y
Kwon
Jungyong
J
Nam
Hong In
HI
Yoon
Kangduk
K
Lee
Dong Goo
DG
Kim
Eunjoon
E
Kim
Chul Hoon
CH
Kim
Jaewon
J
Ko
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2