PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission
Copyright policy )PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission
Significance This paper documents and systematically characterizes the molecular interactions of protein tyrosine phosphatase σ (PTPσ) with glypicans (GPCs). The identified interactions require heparan sulfate (HS), suggesting that GPCs are a major source of HS for PTPσ at excitatory synapses. Strikingly, we found that leucine-rich repeat transmembrane protein 4 (LRRTM4) induces presynaptic differentiation via the PTPσ/GPC interaction, suggesting that PTPσ may function as a coreceptor for GPCs in presynaptic neurons. More importantly, we found that HS-binding ability of PTPσ is critical for excitatory synaptic transmission. These results expand our previous understanding of how synaptic adhesion pathways regulate excitatory synapse development and shed light on GPCs/LRRTM4 trans -synaptic signaling. Moreover, to our knowledge, this is the first study to document the physiological significance of HS in the presynaptic function of mammalian neurons.
- Korean Association Of Science and Technology Studies Korea (Republic of)
- Korea Advanced Institute of Science and Technology Korea (Republic of)
- Shinshu University Japan
- Yonsei University Health System Korea (Republic of)
- Korea University Korea (Republic of)
570, Multiprotein Complexes/metabolism*, Presynaptic Terminals/physiology, Blotting, Western, Genetic Vectors, Oligonucleotides, Presynaptic Terminals, Receptor-Like Protein Tyrosine Phosphatases, 610, Heparitin Sulfate/metabolism, Leucine-Rich Repeat Proteins, glypican, Chromatography, Affinity, Mass Spectrometry, Class 2/metabolism*, Glypicans, Glypicans/metabolism*, Animals, Immunoprecipitation, Chromatography, High Pressure Liquid, In Situ Hybridization, Chromatography, Analysis of Variance, Blotting, Class 2/genetics, Brain, Proteins, LRRTM4, Brain/metabolism*, Immunohistochemistry, Synaptic Transmission/physiology*, Rats, Genetic Vectors/genetics, Affinity, High Pressure Liquid, HEPARAN-SULFATE PROTEOGLYCANS; PROTEIN-TYROSINE PHOSPHATASES; CENTRAL-NERVOUS-SYSTEM; MIDLINE AXON GUIDANCE; ADHESION MOLECULES; TRANSSYNAPTIC INTERACTION; SLIT PROTEIN; LAR; DROSOPHILA; GLYPICANS, Gene Knockdown Techniques, Multiprotein Complexes, synaptic cell adhesion, PTPσ, heparan sulfate, Heparitin Sulfate, Oligonucleotides/genetics, Proteins/metabolism*, Western
570, Multiprotein Complexes/metabolism*, Presynaptic Terminals/physiology, Blotting, Western, Genetic Vectors, Oligonucleotides, Presynaptic Terminals, Receptor-Like Protein Tyrosine Phosphatases, 610, Heparitin Sulfate/metabolism, Leucine-Rich Repeat Proteins, glypican, Chromatography, Affinity, Mass Spectrometry, Class 2/metabolism*, Glypicans, Glypicans/metabolism*, Animals, Immunoprecipitation, Chromatography, High Pressure Liquid, In Situ Hybridization, Chromatography, Analysis of Variance, Blotting, Class 2/genetics, Brain, Proteins, LRRTM4, Brain/metabolism*, Immunohistochemistry, Synaptic Transmission/physiology*, Rats, Genetic Vectors/genetics, Affinity, High Pressure Liquid, HEPARAN-SULFATE PROTEOGLYCANS; PROTEIN-TYROSINE PHOSPHATASES; CENTRAL-NERVOUS-SYSTEM; MIDLINE AXON GUIDANCE; ADHESION MOLECULES; TRANSSYNAPTIC INTERACTION; SLIT PROTEIN; LAR; DROSOPHILA; GLYPICANS, Gene Knockdown Techniques, Multiprotein Complexes, synaptic cell adhesion, PTPσ, heparan sulfate, Heparitin Sulfate, Oligonucleotides/genetics, Proteins/metabolism*, Western
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