The γ subunits of voltage-dependent calcium channels influence calcium current properties and may be involved in other physiological functions. Five distinct γ subunits have been described from human and/or mouse. The first identified member of this group of proteins, γ1, is a component of the L-type calcium channel expressed in skeletal muscle. A second member, γ2, identified from the stargazer mouse regulates the targeting of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors to the postsynaptic membrane. We report here the identification of three novel γ subunits from rat and mouse as well as the unidentified rat, mouse and human orthologs of the previously described subunits. Phylogenetic analysis of the 24 mammalian γ subunits suggests the following relationship ((((γ2, γ3), (γ4, γ8)), (γ5, γ7)), (γ1, γ6)) that indicates that they evolved from a common ancestral γ subunit via gene duplication. Our analysis reveals that the novel γ subunit γ6 most closely resembles γ1 and shares with it the lack of a PSD-95/DLG/ZO-1 (PDZ)-binding motif that is characteristic of most other γ subunits. Rat γ subunit mRNAs are expressed in multiple tissues including brain, heart, lung, and testis. The expression of γ1 mRNA and the long isoform of γ6 mRNA is most robust in skeletal muscle, while γ6 is also highly expressed in cardiac muscle. Based on our analysis of the molecular evolution, primary structure, and tissue distribution of the γ subunits, we propose that γ1 and γ6 may share common physiological functions distinct from the other homologous γ subunits.
- Cardiac muscle
- Gene duplication
- Phylogenetic analysis
- Voltage-dependent ion channels
ASJC Scopus subject areas