Conservation of the developmentally regulated dendritic localization of a Purkinje cell-specific mRNA that encodes a G-protein modulator: comparison of rodent and human Pcp2(L7) gene structure and expression.

摘要

L7/Pcp-2 is a GoLoco domain protein that modulates the activation of Galpha(i) and Galpha(o). We have previously described the Purkinje cell-specific expression of the Pcp-2(L7) gene and the abundant localization of its mRNA in mouse cerebellar Purkinje cell dendrites. Here we report on two alternative cerebellar forms of the L7/Pcp-2 mRNA and protein by examination of the gene structures and cDNA sequences of the mouse, rat, and human genes. The structures of the rodent and human genes are very similar with the most notable difference in the genomic configuration of the first exon. Despite this difference, the human and rodent genes both encode two alternative mRNAs due to the choice of two transcriptional start positions. The two mRNA forms, in turn, predict two forms of the L7/Pcp-2 protein, which are both highly conserved across species. These two protein forms differ with respect to the number of GoLoco domains. Lastly we examined the issue of mRNA localization in dendrites. In mouse both mRNA forms are detectable in dendrites but their relative proportions change during development. In addition we performed in situ hybridization on a developmental series of human cerebellar sections and demonstrate that the L7/Pcp-2 mRNA is also localized in dendrites of humans. As previously described in the mouse the dendritic localization in humans is developmentally regulated being most prominent during the peak phase of synaptogenesis and decreasing dramatically with age. The conservation of all of these properties of both the L7/Pcp-2 protein and mRNA highlights their likely importance in controlling the development and/or motor control function of Purkinje cells.