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Endosomal trafficking of AMPA receptors in frontal cortex of elderly patients with schizophrenia.

Abstract
Several lines of evidence indicate altered trafficking of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors in schizophrenia. Previous reports have implicated alterations in the endosomal trafficking of AMPA receptors in this illness. We hypothesized that late endosome content of AMPA receptor subunits is altered in schizophrenia. Accordingly, we developed a technique to isolate and measure contents of late endosomes from postmortem human tissue. We found no changes in the expression of the AMPA subunits, GluR1-4, in late endosomes from the dorsolateral prefrontal cortex in schizophrenia. We also hypothesized that proteins involved in the sorting and trafficking of AMPA receptors between endosomal compartments would be altered in schizophrenia. We found no changes in expression of multiple proteins associated with these processes (dynamin3, Arc/ARG3.1, NEEP21, GRASP1, liprin α, and syntaxin13). Together, these data suggest that endosomal trafficking of AMPA receptors in the prefrontal cortex may be largely intact in schizophrenia.
AuthorsJohn C Hammond, Robert E McCullumsmith, Vahram Haroutunian, James H Meador-Woodruff
JournalSchizophrenia research (Schizophr Res) Vol. 130 Issue 1-3 Pg. 260-5 (Aug 2011) ISSN: 1573-2509 [Electronic] Netherlands
PMID21576009 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • GRIP1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • rab7 GTP-Binding Proteins
  • N-Ethylmaleimide-Sensitive Proteins
  • rab GTP-Binding Proteins
Topics
  • Adaptor Proteins, Signal Transducing (metabolism)
  • Aged
  • Aged, 80 and over
  • Carrier Proteins (metabolism)
  • Discs Large Homolog 1 Protein
  • Endosomes (metabolism)
  • Female
  • Frontal Lobe (metabolism, ultrastructure)
  • Humans
  • Male
  • Membrane Proteins (metabolism)
  • Microscopy, Electron, Transmission (methods)
  • Middle Aged
  • Models, Biological
  • N-Ethylmaleimide-Sensitive Proteins (metabolism)
  • Nerve Tissue Proteins (metabolism)
  • Protein Transport (physiology)
  • Receptors, AMPA (metabolism)
  • Schizophrenia (pathology)
  • rab GTP-Binding Proteins (metabolism)
  • rab7 GTP-Binding Proteins

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