Disease relevance of Ggamma1

• Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease [1].

High impact information on Ggamma1

• These results are consistent with the hypothesis that Ggamma1 participates in the signal transduction of sugar taste reception [2].
• RNA interference targeting to the Ggamma1 gene reduced the amount of Ggamma1 mRNA and suppressed electrophysiological response of the sugar receptor neuron [2].
• This mutant fails to bind Gbeta13F to the membrane, indicating an essential role of cortical Ggamma1-Gbeta13F signaling in asymmetric divisions [3].
• In the transgenic flies, mutated Ggammae forms a dimeric complex with Gbetae, with the consequence that the fraction of non-membrane-bound Gbetagamma is increased [4].
• Thus, farnesylation of Ggammae facilitates the membrane attachment of the Gbetagamma complex [4].

Biological context of Ggamma1

• We identified here the first Drosophila mutant in the Ggamma1 subunit of heterotrimeric G protein, which produces Ggamma1 lacking its membrane anchor site and exhibits phenotypes identical to those of Gbeta13F, including abnormal spindle asymmetry and spindle orientation in NB divisions [3].
• Genomic Southern blot hybridization indicated that the Drosophila genome has only one D-G gamma 1 gene [5].
• The spatial expression pattern determined for Ggamma(e) as well as co-immunoprecipitation experiments demonstrated that Ggamma(e) dimerizes with Gbeta(e) to form the heterodimeric Gbetagamma subunit which functions in visual transduction in the Drosophila compound eye [6].
• The Galpha and Gbetagamma components of heterotrimeric G proteins, typically associated with cell-surface receptor signaling, also partake in the macromolecular interactions that underlie cell polarity and cell division [7].

Anatomical context of Ggamma1

• As is the case for the other G protein genes of Drosophila, the D-G gamma 1 gene is predominantly expressed in the central nervous system of the fly [5].

Associations of Ggamma1 with chemical compounds

• The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1 [1].
• The GoLoco motif was recently identified as a selective Galpha-binding partner: the GoLoco-Galpha interaction can displace Gbetagamma and inhibit guanine nucleotide release from the bound Galpha subunit [7].

Other interactions of Ggamma1

• This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis [1].
• GPCRs act on inactive Galpha.GDP/Gbetagamma heterotrimers to promote GDP release and GTP binding, resulting in liberation of Galpha from Gbetagamma [8].

Analytical, diagnostic and therapeutic context of Ggamma1

• Nucleotide (nt) sequence analysis showed that the 70-amino-acid polypeptide encoded by the 1.3-kb transcript of D-G gamma 1 is the same as that encoded by the 1.1- and 2.6-kb D-G gamma 1 transcripts reported earlier [Ray and Ganguly, J. Biol. Chem. 267 (1992) 6086-6092] [9].

References