Spatial diversity in gene expression for VDCCγ subunit family in developing and adult mouse brains

Abstract

The γ subunit of voltage-dependent Ca 2+ channels (VDCCs) is characterized by molecular diversity and regulation of AMPA-type glutamate receptors as well as VDCCs. In the present study, we examined expressions for the VDCCγ1-8 subunit mRNAs in developing and adult mouse brains by in situ hybridization. In adult brains, the γ2 and γ7 subunit mRNAs were widely expressed in various grey matter regions with the highest level in cerebellar Purkinje cells and granule cells. The γ3 and γ8 subunit mRNAs predominated in the telencephalon, with the latter being at striking levels in the hippocampus. The γ4 subunit mRNA was enriched in the olfactory bulb, striatum, thalamus, and hypothalamus. The γ5 subunit mRNA was abundant in the olfactory bulb, hippocampal CA2, thalamus, inferior colliculus, andBergmann glia. Transcripts of these subunits were detected in embryonic brains: some showed well-preserved spatial patterns (γ2, γ5, γ7 and γ8), while others underwent developmental up-(γ3) or down-regulation (γ4). In contrast, the γ1 and γ6 subunit mRNAs were negative or very low throughout brain development. Therefore the present study has revealed spatial diversity in gene expression for individual VDCCγ subunits, presumably reflecting functional diversity of this protein family and their differential involvement in neural function.

New Transmembrane AMPA Receptor Regulatory Protein Isoform, γ-7, Differentially Regulates AMPA Receptors

“…On the contrary, ␥-5 is enriched in microsomal fraction (P3) and synaptosomal fraction but not in the PSD. This observation is consistent with the report that ␥-5 is mainly expressed in cerebellar Bergmann glia (Fukaya et al, 2005), which lack a PSD domain. As controls, we show that PSD-95 and synaptophysin are enriched in the PSD and synaptic vesicle fractions, respectively.…”

“…Mice lacking ␥-8 have an 80 -90% decrease in extrasynaptic AMPA receptor in hippocampal neurons (Rouach et al, 2005;Fukaya et al, 2006). The residual AMPA receptor function in the hippocampus of ␥-8 knockouts likely reflects expression of ␥-2 and ␥-3 in these neurons (Fukaya et al, 2005). The finding that AMPA receptor responses are present in cerebellar Purkinje cells of stargazer mice has been perplexing because only ␥-2, and not ␥-3, ␥-4 or ␥-8, occurs in these neurons (Fukaya et al, 2005).…”

“…The residual AMPA receptor function in the hippocampus of ␥-8 knockouts likely reflects expression of ␥-2 and ␥-3 in these neurons (Fukaya et al, 2005). The finding that AMPA receptor responses are present in cerebellar Purkinje cells of stargazer mice has been perplexing because only ␥-2, and not ␥-3, ␥-4 or ␥-8, occurs in these neurons (Fukaya et al, 2005). Our identification of ␥-7 as a new TARP enriched in Purkinje cells likely explains this functional redundancy and the presence of AMPA receptor function in Purkinje cells of stargazer mice.…”

Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior

“…On the basis of in situ hybridization and immunohistochemistry, γ-7 is expressed in other cerebellar neuronal cell types including stellate cells (SCs) and granule neurons (CGNs) (11,12,14). Biochemical and heterologous expression studies have shown that γ-7 is capable of binding to AMPARs and enhancing AMPAR trafficking and gating in stg CGNs, albeit less effectively than γ-2 (12, 16).…”

“…Of particular interest is TARP γ-7, which is expressed throughout the brain but exhibits high levels of expression, along with γ-2, in cerebellar Purkinje cells (PCs) (11)(12)(13)(14). Deleting γ-2 on its own causes a ∼60% reduction in AMPAR-mediated synaptic currents in PCs (14,15).…”