Disease relevance of Gnb5

• Group B streptococcus (GBS; Streptococcus agalactiae) induces apoptosis of macrophages, and this may be an important mechanism GBS uses to suppress immune responses [1].
• PTF was administered intraperitoneally at a dose of 1 mg/mouse (50 mg/kg of body weight) 1 h after GBS infection and then at 24-h intervals for 4 days [2].
• Intravenous inoculation of CD1 mice with 10(7) CFU of type IV group B Streptococcus (GBS IV) results in a high incidence of diffuse septic arthritis [2].
• GBS type III CPS was conjugated to tetanus toxoid (TT) or recombinant cholera toxin B subunit (rCTB) either directly or to rCTB indirectly via TT [3].
• Native and recombinant Gbeta5 and/or R7 expression have been studied in model systems like rat pheochromocytoma PC12 cells where their nuclear localization can be studied by fluorescence microscopy and/or subcellular fractionation [4].

Psychiatry related information on Gnb5

• Cellular and humoral aspects of host defense mechanisms against GBS [5].

High impact information on Gnb5

• Consistent with this notion, we have found that elevation of RGS9-1 mRNA levels by transgene expression does not increase RGS9-1 protein level in the retina, suggesting that Gbeta5 levels may be limiting [6].
• The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport [7].
• In addition to the plasma membrane, a large portion of RGS9-2 was found in the neuronal specializations, the postsynaptic densities, where it forms complexes with R7BP and its constitutive partner Gbeta5 [8].
• We found that RACK1 interacts with several different G betagamma isoforms, including G beta1gamma1, Gbeta1gamma2, and Gbeta5gamma2, with similar affinities, suggesting that the conserved residues between G beta1 and G beta5 may be involved in their binding to RACK1 [9].
• We found that light responses from R9AP knockout rods were very slow to recover and were indistinguishable from those of RGS9 or Gbeta5 knockout rods [10].

Biological context of Gnb5

• Using a transient cotransfection assay, we showed that a plasmid construct expressing the G beta 5 open reading frame, when coexpressed with different G-protein gamma (G gamma)-subunits, can stimulate the activity of the beta 2 isoform of phosphoinositide-specific phospholipase C (PLC beta 2) [11].
• Both RGS9-/- and Gbeta5-/- responses were consistent with another factor weakly regulating GTP hydrolysis by transducin in a manner proportional to the inward current [12].
• The mechanisms whereby GBS induces apoptosis have not been identified [1].
• We studied GBS infection in murine macrophage-like J774A.1 cells and analyzed gene expression before apoptosis [1].
• Our findings suggest that priming with CPS affects the distribution of IgG subclasses to GBS CPS and that pre-existing anti-carrier rCTB immunity can have an inhibitory effect on mucosal immune responses elicited by the conjugate vaccine given by the i.n. route [13].

Anatomical context of Gnb5

• Expression of Gnb5 in adult tissues was detected preferentially in testes, in both hamsters and humans [14].
• HMDMs and murine macrophages are killed by GBS by alternative, NO-independent mechanisms [1].
• At 2 days after commencing sustained morphine treatment, the levels of mRNA for RGS7, RGS9-2, RGS11, and Gbeta5 increased in most of the brain structures studied (striatum, thalamus, periaqueductal gray matter (PAG), and cortex) [15].
• In the spinal cord Gbeta5 in contrast to Gbeta2 concentrates around alpha-motoneurons [16].
• The different subcellular distribution of Gbeta-subunits in cultivated neurons reflects that observed in tissue where Gbeta5 and Gbeta2 associate preferentially with the perikarya and the neuropil, respectively, and suggests an additional association of Gbeta2 with secretory vesicles [16].

Associations of Gnb5 with chemical compounds

• This novel gene, named Gnb5, for guanine nucleotide-binding protein, beta 5, codes for a protein of 538 amino acids with a highly acidic amino terminus containing a proline-rich domain, followed by a neutral domain with five repeat units of the beta-transducin (WD-40) motif [14].
• GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease [17].
• Expression of neural RGS-R7 and Gbeta5 Proteins in Response to Acute and Chronic Morphine [15].
• NMMA did not impair the microbicidal activity of macrophages, however, and SNAP was not bactericidal against GBS in vitro [1].
• Cytokine levels were quantified in the serum and joints by enzyme-linked immunosorbent assay in mice injected with GBS IV and tested or not tested with pentoxifylline (PTF), a methylxanthine that affects cytokine production [2].

Physical interactions of Gnb5

• In retina, Gbeta5 has been isolated in a soluble complex with regulator of G-protein signaling RGS7 [18].

Other interactions of Gnb5

• We have identified a fifth member of the G-protein beta-subunit family, G beta 5, by molecular cloning [11].

Analytical, diagnostic and therapeutic context of Gnb5

• Northern blot analysis of poly(A)-selected mRNA prepared from different mouse tissues demonstrated that G beta 5 is predominantly expressed in adult brain as two transcripts of 2.3 and 1.75 kilobases [11].
• An intraperitoneal injection of GBS organisms and protective antiserum from a single syringe can be used to create an animal model of disease [19].
• Our findings favour dot blotting as the method of choice although we consider all three methods acceptable for serotyping of GBS [20].
• Subcellular fractionation allows isolation of a purified nuclear fraction that can be probed for the presence of Gbeta5 and/or R7 subunits by immunoblots or immunoprecipitation and compared to other subcellular fractions [4].
• Nucleic acid counterstains chosen for compatibility with the fluorescent tags on secondary antibodies can facilitate the assay of R7/Gbeta5 nuclear localization by epifluorescence or confocal laser microscopy [4].

References