title: 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.
authors.affiliation: Department of Neurobiology, University of Alabama Birmingham, Birmingham, AL 35294-0021, United States. hammondj@uab.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Hammond
authors.forename: Robert E
authors.initials: RE
authors.lastname: McCullumsmith
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008875:Middle Aged; D008954:Models, Biological; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C491310:GRIP1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000090802:rab7 GTP-Binding Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D020691:rab GTP-Binding Proteins