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. 2015 Aug 4;5(8):e612. doi: 10.1038/tp.2015.102

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Copyright © 2015 Macmillan Publishers Limited

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The β2 GABA_AR subunit is abnormally expressed in an isoform-specific manner and the ratios of β1 and β2 subunit isoforms are altered in the ER in schizophrenia. Western blot analysis of total β2 GABA_AR subunit (β2_ALL) and individual β2 GABA_AR subunit 50 kDa and 48 kDa isoforms (β2_50 kDa and β2_48 kDa, respectively), the ratios of β2 GABA_AR subunit isoforms to each other, and the ratio of β1:β2 GABA_AR subunit and subunit isoform expression in the ER fraction in schizophrenia and comparison subjects. (a) ER fraction-normalized expression of β2_ALL, and specifically the β2_50 kDa GABA_AR subunit isoform, is increased in schizophrenia. (b) The ratio of β2_48 kDa:β2_ALL GABA_AR subunit fraction-normalized expression is decreased in the ER in schizophrenia. (c) The ratio of β2_50 kDa:β2_48 kDa GABA_AR subunit fraction-normalized signal intensities is increased in schizophrenia. (d) Representative images of western blots of the β2 GABA_AR subunit, VCP and JM4 from the ER fraction from comparison and schizophrenia subjects with the β2_50 kDa and β2_48 kDa protein bands indicated. (e) The ratio of β1:β2_ALL, and specifically the ratio of β1:β2_50 kDa GABA_AR subunit expression is significantly less in the ER fraction in schizophrenia. Data are expressed as either the signal intensity of protein targets in the ER fraction normalized to VCP as a loading control and JM4 as an ER marker relative to the VCP-normalized signal intensity of the same target in the total homogenate, or expressed as a ratio of normalized signal intensities, for each data point with means±s.e.m. for each group indicated in a, b, c and e. *P<0.05, **P<0.01. COMP, comparison subject; ER, endoplasmic reticulum; GABA_AR, γ-aminobutyric acid type A receptor; SCZ, schizophrenia; VCP, valosin-containing protein.