Disease relevance of GNAZ

• A series of primary rhabdoid tumors with chromosome 22q11 deletions were screened for mutations in the coding sequences of RTDR1, GNAZ and RAB36, but did not demonstrate any disease-specific alterations [1].
• Identification of Gz alpha as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes [2].
• By light microscopy, Gz-alpha was localized to the cytoplasm of neurons, with predominant reactivity in ganglion cells of the retina, Purkinje cells of the cerebellum, and most neurons of the hippocampus and cerebral cortex [3].
• Western-blot analysis of human neuroblastoma SH-SY5Y cells (mu- and delta-receptors) revealed the presence of the following G-protein subunits: Gi alpha 1, Gi alpha 2, Gs alpha, G(o) alpha, Gz alpha, and G beta, a pattern resembling that observed in central nervous tissue [4].
• While by in vitro mutagenesis it has been demonstrated that activated mutant of Gq alpha, G12alpha, G13alpha and Gz alpha are fully oncogenic, it remains to be proved whether or not these abnormalities might naturally occur in human tumors and, in particular, in pituitary adenomas [5].

Psychiatry related information on GNAZ

• Analysis of GNAZ gene polymorphism in bipolar affective disorder [6].

High impact information on GNAZ

• Both adult and fetal human RPE cells contain mRNA for multiple G protein alpha subunits (G alpha) including Gs alpha, Gi-1 alpha, Gi-2 alpha, Gi-3 alpha, and Gz alpha (or Gx alpha), where Gs and Gi are proteins that stimulate or inhibit adenylyl cyclase, respectively, and Gz is a protein that may mediate pertussis toxin-insensitive events [7].
• The deduced amino acid sequence of Gz alpha is 41-67% identical with those of other known G-protein alpha subunits [8].
• In a further study of G-protein diversity and signal transduction in the retina, we have identified a G-protein alpha subunit, which we refer to as Gz alpha, by isolating a human retinal cDNA clone that cross-hybridizes at reduced stringency with bovine Tr alpha-subunit cDNA [8].
• RNA encoding Gz alpha was also detected in individual human megakaryocytes by in situ hybridization [2].
• The paucity of Gz alpha protein and RNA in the megakaryoblastic cell lines suggests that either there has been a selective loss of the ability to synthesize Gz alpha from these cells or that Gz alpha appears at a later stage in megakaryocyte development than does Gi alpha [2].

Biological context of GNAZ

• These data continue to provide some support for a BPD susceptibility gene on 22q11, possibly in linkage disequilibrium with the GNAZ 309 polymorphism [6].
• We suggest that Gz alpha, which appears to be highly expressed in neural tissues, represents a member of a subfamily of G proteins that mediate signal transduction in pertussis toxin-insensitive systems [8].
• Recently, a cDNA coding for a novel G protein alpha-subunit, Gz-alpha, was isolated from a human retinal cDNA library and shown by Northern blot analysis to be expressed at high levels in neural tissues [3].
• Novel conserved synteny between human chromosome 22 and cattle chromosome 22 established by linkage mapping of transducin alpha-1 subunit (GNAZ) [9].
• We show here that under conditions promoting phorbol 12-myristate 13-acetate-stimulated phosphorylation of Gz alpha in permeabilized platelets, Gq alpha is not phosphorylated [10].

Anatomical context of GNAZ

• GNAZ in human fetal cochlea: expression, localization, and potential role in inner ear function [11].
• To address the potential role of G proteins expressed in human fetal cochlea, degenerate oligonucleotide primers corresponding to the 3'-end of the conserved region of alpha-subunits were used for polymerase chain reaction amplification of reverse-transcribed total human fetal cochlear mRNAs; GNAZ and GNAQ were isolated [11].
• Thus, based on immunoreactivity and nucleotide sequencing, platelets and megakaryocytes contain substantial quantities of a protein identical to brain and retinal Gz alpha [2].
• Three different Gz alpha-selective antisera reacted with a 40-Kd protein in platelet membranes [2].
• Reactivity was confined to perikaryon, dendrites, and a very short segment of proximal axons, except for the retinal ganglion cells, in which the axons in the nerve fiber layer showed intense Gz-alpha immunoreactivity proximal to the lamina cribrosa [3].

Associations of GNAZ with chemical compounds

• A focus was placed on Ser25 and Ser27, the 2 serine residues within a sequence of Gz alpha used to obtain a phosphorylation-sensitive antibody [10].
• Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain [12].
• Gz alpha variants containing selected substitutions of alanine for serine residues were expressed in human kidney 293 cells, and the ability of each to be phosphorylated in response to phorbol 12-myristate 13-acetate was examined [10].
• We have demonstrated previously by phosphoamino acid analysis and CNBr peptide mapping that phosphorylation occurs at a serine residue(s) within the NH2-terminal 53 residues of Gz alpha [10].
• We have demonstrated previously that the G protein alpha subunit Gz alpha (or Gx alpha) in human platelets is subject to phosphorylation by agents that activate protein kinase C, including phorbol 12-myristate 13-acetate, thrombin, and the thromboxane A2 analog U46619 [13].

Regulatory relationships of GNAZ

• GNAZ is expressed in high levels in neural tissue while GNAQ is ubiquitously expressed [11].

Other interactions of GNAZ

• Recent studies have shown that human retina and rat brain contain mRNA encoding a novel 40-Kd G protein alpha subunit referred to as Gz alpha [2].
• Recombinant Gi alpha 1, Gi alpha 2, Gi alpha 3, Go alpha (A), Gs alpha, and Gz alpha all failed to stimulate any of the isoforms of PLC [14].

Analytical, diagnostic and therapeutic context of GNAZ

• We characterized GNAZ expression using Northern blots, tissue in-situ hybridization and immunohistochemistry techniques to elucidate the potential role of this protein in inner ear function [11].
• Northern blotting with a Gz alpha-specific probe prepared from retinal Gz alpha showed two hybridizing species in platelet RNA: a major band at 3.5 kb and a minor band at 2.2 kb [2].
• Pre-embedding immunoelectron microscopy demonstrated the presence of focal Gz-alpha immunoreactivity on the nuclear membranes, endoplasmic reticulum, and plasma membranes of Purkinje cell perikarya and in association with microtubules in their proximal dendrites [3].
• Anti-Gz alpha caused immunoprecipitation of 24.2 +/- 5.2% of G protein-associated D5 receptors, indicating coupling between D5 and Gz alpha [15].
• Analysis of Gz alpha by site-directed mutagenesis. Sites and specificity of protein kinase C-dependent phosphorylation [10].

References