Cited 20 time in webofscience Cited 22 time in scopus

PTP sigma Drives Excitatory Presynaptic Assembly via Various Extracellular and Intracellular Mechanisms

Title
PTP sigma Drives Excitatory Presynaptic Assembly via Various Extracellular and Intracellular Mechanisms
Authors
Han, Kyung AhKo, Ji SeungPramanik, GopalKim, Jin YoungTabuchi, KatsuhikoUm, Ji WonKo, Jaewon
DGIST Authors
Um, Ji WonKo, Jaewon
Issue Date
2018-07
Citation
Journal of Neuroscience, 38(30), 6700-6721
Type
Article
Article Type
Article
Keywords
LAR-RPTPSPresynaptic assemblyProteinProtein interactionPTPσSynaptic adhesion moleculePROTEIN-TYROSINE-PHOSPHATASESLIPRIN-ALPHA PROTEINSSYNAPSE FORMATIONACTIVE ZONELAR-RPTPSTRANSSYNAPTIC INTERACTIONMOLECULAR-MECHANISMSADHESION MOLECULESSTRUCTURAL BASISRECEPTOR
ISSN
0270-6474
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/9238
DOI
10.1523/JNEUROSCI.0672-18.2018
Publisher
Society for Neuroscience
Related Researcher
  • Author Ko, Jaewon Laboratory of Synapse Formation and Function
  • Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
Files:
There are no files associated with this item.
Collection:
Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE