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PTP sigma Drives Excitatory Presynaptic Assembly via Various Extracellular and Intracellular Mechanisms
- PTP sigma Drives Excitatory Presynaptic Assembly via Various Extracellular and Intracellular Mechanisms
- Han, Kyung Ah; Ko, Ji Seung; Pramanik, Gopal; Kim, Jin Young; Tabuchi, Katsuhiko; Um, Ji Won; Ko, Jaewon
- DGIST Authors
- Um, Ji Won; Ko, Jaewon
- Issue Date
- Journal of Neuroscience, 38(30), 6700-6721
- Article Type
- LAR-RPTPS; Presynaptic assembly; Protein; Protein interaction; PTPσ; Synaptic adhesion molecule; PROTEIN-TYROSINE-PHOSPHATASES; LIPRIN-ALPHA PROTEINS; SYNAPSE FORMATION; ACTIVE ZONE; LAR-RPTPS; TRANSSYNAPTIC INTERACTION; MOLECULAR-MECHANISMS; ADHESION MOLECULES; STRUCTURAL BASIS; RECEPTOR
- Leukocyte common antigen-receptor protein tyrosine phosphatases (LAR-RPTPs) are hub proteins that organize excitatory and inhibitory synapse development through binding to various extracellular ligands. Here, we report that knockdown (KD) of the LAR-RPTP family member PTPσ reduced excitatory synapse number and transmission in cultured rat hippocampal neurons, whereas KD of PTPδ produced comparable decreases at inhibitory synapses, in both cases without altering expression levels of interacting proteins. An extensive series of rescue experiments revealed that extracellular interactions of PTPσ with Slitrks are important for excitatory synapse development. These experiments further showed that the intracellular D2 domain of PTPσ is required for induction of heterologous synapse formation by Slitrk1 or TrkC, suggesting that interaction of LAR-RPTPs with distinct intracellular presynaptic proteins, drives presynaptic machinery assembly. Consistent with this, double-KD of liprin-α2 and-α3 or KD of PTPσ substrates (N-cadherin and p250RhoGAP) in neurons inhibited Slitrk6-induced, PTPσ-mediated heterologous synapse formation activity. We propose a synaptogenesis model in presynaptic neurons involving LAR-RPTP-organized retrograde signaling cascades, in which both extracellular and intracellular mechanisms are critical in orchestrating distinct synapse types. © 2018 the authors.
- Society for Neuroscience
- Related Researcher
Laboratory of Synapse Formation and Function
Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
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- Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles
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