Structural Basis for LAR-RPTP-Mediated Synaptogenesis

Mol Cells. 2018 Jul 31;41(7):622-630. doi: 10.14348/molcells.2018.0202. Epub 2018 Jul 11.

Abstract

Leukocyte common antigen-related protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that regulate neurite outgrowth and neuronal regeneration. LAR-RPTPs have also received particular attention as the major presynaptic hubs for synapse organization through selective binding to numerous postsynaptic adhesion partners. Recent structural studies on LAR-RPTP-mediated trans-synaptic adhesion complexes have provided significant insight into the molecular basis of their specific interactions, the key codes for their selective binding, as well as the higher-order clustering of LAR-RPTPs necessary for synaptogenic activity. In this review, we summarize the structures of LAR-RPTPs in complex with various postsynaptic adhesion partners and discuss the molecular mechanisms underlying LAR-RPTP-mediated synaptogenesis.

Keywords: LAR-RPTPs; LAR-RPTP–mediated trans-synaptic adhesion complex; heparan sulfate; higher-order clustering; synaptic adhesion molecules.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Models, Molecular
  • Neurogenesis*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / chemistry*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
  • Structure-Activity Relationship
  • Synapses / metabolism*

Substances

  • Receptor-Like Protein Tyrosine Phosphatases, Class 2