Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain

Eur J Neurosci. 2002 May;15(9):1493-8. doi: 10.1046/j.1460-9568.2002.01987.x.

Abstract

Membrane-associated guanylate kinase-interacting protein (MAGUIN) has been identified as a protein binding postsynaptic density (PSD)-95 and synaptic scaffolding molecule (S-SCAM). MAGUIN has one sterile alpha motif, one conserved region in connector enhancer of ksr (Cnk) (CRIC), one PSD-95/Dlg-A/ZO-1 (PDZ) and one pleckstrin homology (PH) domain. There are two isoforms, MAGUIN-1 and -2. MAGUIN-1 binds the PDZ domains of PSD-95 and S-SCAM by the C-terminus, whereas MAGUIN-2 does not bind to PSD-95 or S-SCAM. Here, we have determined that MAGUIN-2 is also localized at synapses and that the synaptic localization of MAGUIN depends on the pleckstrin homology domain. The overexpressed C-terminal PDZ-binding region inhibits the synaptic targeting of PSD-95. Furthermore, the synaptic targeting of MAGUIN does not require N-methyl-d-aspartate (NMDA) receptor activity. These findings suggest that MAGUIN-1 and -2 are recruited to synapses by the PH domain and that MAGUIN-1 subsequently interacts with PSD-95 at synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Blood Proteins / metabolism
  • Carrier Proteins / metabolism*
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cricetinae
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Disks Large Homolog 4 Protein
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Fetus
  • Green Fluorescent Proteins
  • Hippocampus / embryology*
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Indicators and Reagents / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins / metabolism
  • Macromolecular Substances
  • Membrane Proteins
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Phosphoproteins / metabolism
  • Pregnancy
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / metabolism
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure
  • Synaptic Transmission / physiology*
  • Synaptophysin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Blood Proteins
  • Carrier Proteins
  • Cnksr2 protein, rat
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Excitatory Amino Acid Antagonists
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Macromolecular Substances
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Receptors, Glutamate
  • Synaptophysin
  • platelet protein P47
  • postsynaptic density proteins
  • Green Fluorescent Proteins