A further limitation of this study is the absence of a direct assay of α5 protein in brain tissue. There are several caveats when mRNA transcript level is used as a proxy for functional receptor number. The mRNA level largely reflects the content of the somato-dendritic compartment, while it is very likely that most receptors incorporating the α5 subunit are located in the terminal regions of the cell [35]. Further, it is known that the number of receptors containing a subunit protein can change by up to 2-fold in the absence of a change in mRNA content (for example, a study by Pauly et al)[36]. Finally, the amount of α5 subunit protein available has been shown to strongly influence the assembly of receptors containing α4 and β2 subunits [37] and so the ultimate level of functional receptors containing the α5 subunit may be influenced by additional factors. Because of these factors it is not possible to directly link our measured effects on transcription to a predicted change in the availability of functional cell-surface receptors containing the α5 subunit. However, a reduction in transcript availability has the potential to have widespread effects on the number and subunit stoichiometry of surface receptors.
