Disease relevance of RGS12

• Using primary dorsal root ganglion neurons in culture, here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel [1].
• Silence of RGS12 expression using vector and lentivirus based RNA interference (RNAi) impaired phosphorylation of phospholipase C (PLC)gamma and blocked [Ca(2+)](i) oscillations, NFAT2 expression, and osteoclast differentiation in RANKL-induced RAW264.7 cells and BMMs [2].

High impact information on RGS12

• Inhibition of endogenous RGS12, a member of the family of regulators of G-protein signalling, selectively alters the time course of voltage-independent inhibition [1].
• Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel [1].
• Here, we describe functional characterization of the GoLoco motif regions of RGS12 and RGS14 [3].
• RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity [3].
• Novel alternative splicing and nuclear localization of human RGS12 gene products [4].

Biological context of RGS12

• Here, we report identification of 12 distinct transcripts of human RGS12 that arise by unusually complex splicing of the RGS12 gene, which spans 70 kilobase pairs of genomic DNA and contains 16 exons [4].
• We have also identified the human orthologue of rRgs12 by alignment of cosmid sequences in the database which map the human RGS12 gene to chromosome 4p16 [5].
• We have also identified conserved regions in RGS12 which are similar to protein domains found in mouse rhophilin and coiled-coil proteins suggesting possible interactions with ras-like G-proteins [5].
• To study the role of the RGS12 in osteoclast differentiation, we used vector and lentivirus-based RNAi gene silencing technology to silence the RGS12 gene in the monocyte progenitor cell lines and primary bone marrow-derived monocytes (BMMs) [2].

Anatomical context of RGS12

• Expression of RGS12 proteins with long and intermediate C-terminal domains was not observed in COS-7 cells, suggesting that 3'-splicing of RGS12 transcripts may influence the expression or stability of the encoded proteins [4].
• RGS12 Is Essential for RANKL-Evoked Signaling for Terminal Differentiation of Osteoclasts In Vitro [2].
• In airway smooth muscle cells, over-expressed recombinant RGS12 and the isolated PDZ/PTB domain N-terminus co-localised with PDGFbeta receptor in cytoplasmic vesicles [6].
• Non-nuclear staining for RGS12 was also evident in thalamus of adult monkey brain; however, in 1-month-old monkey brain, it was seen into two different populations, one with nuclear and the other with cytoplasmic staining [7].
• In contrast to RGS12 protein, RGS14 was localized in astrocytes in addition to neurons [7].

Physical interactions of RGS12

• Molecular cloning of regulators of G-protein signaling family members and characterization of binding specificity of RGS12 PDZ domain [8].

Other interactions of RGS12

• The effect of RGS12 on PDGFbeta receptor signalling to p42/p44 mitogen activated protein kinase in mammalian cells [6].

Analytical, diagnostic and therapeutic context of RGS12

• The interaction between RGS12 and N-type calcium channels was elucidated using co-immunoprecipitation and immunoblotting [2].

References