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PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic

Ji Seung Ko1, Gopal Pramanik2, Ji Won Um1

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;

Proceedings of the National Academy of Sciences of the United States of America
|January 28, 2015
PubMed

Insights

Glypican 4 (GPC-4) is identified as a key binding partner for PTPσ, a protein tyrosine phosphatase. This interaction is crucial for maintaining excitatory synapse development and function in the brain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR, PTPδ, PTPσ) are critical synaptic adhesion molecules.
  • These phosphatases play a vital role in organizing synapse development and function.

Purpose of the Study:

  • To identify ligands for PTPσ.
  • To elucidate the role of PTPσ and its ligand in synaptic organization and function.

Main Methods:

  • Ligand identification using biochemical assays.
  • Analysis of protein-protein interactions between PTPσ, glypican 4 (GPC-4), and leucine-rich repeat transmembrane protein 4 (LRRTM4).
  • Synapse formation assays using neuronal cultures with single knockdown (KD) of PTPσ and LAR.
  • Electrophysiological recordings to assess excitatory synaptic transmission.

Main Results:

  • Glypican 4 (GPC-4) was identified as a high-affinity, heparan sulfate (HS)-dependent ligand for PTPσ.
  • PTPσ formed complexes with cleaved GPC-4 and LRRTM4 in rat brains.
  • Knockdown of PTPσ, but not LAR, impaired LRRTM4-mediated synaptogenic activity and significantly reduced excitatory synaptic transmission frequency and amplitude.
  • A HS-binding-defective PTPσ mutant failed to rescue these deficits.

Conclusions:

  • Presynaptic PTPσ and its ligand GPC-4 interact in a HS-dependent manner to regulate excitatory synapse development.
  • This PTPσ-GPC-4 pathway is essential for maintaining the structure and function of excitatory synapses.

Keywords:
LRRTM4PTPσglypicanheparan sulfatesynaptic cell adhesion

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