Disease relevance of PDC

• We investigated the phenotype and frequency of circulating myeloid dendritic cells (MDC) and plasmacytoid DC (PDC) in 86 multiple sclerosis (MS) patients and 33 healthy controls (HC) [1].
• Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) is a unique neurodegenerative disease found on the island of Guam [2].
• Commentary on: return of the cycad hypothesis - does the amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health [3]?
• In paroxysmal dystonic choreoathetosis/non-kinesigenic dyskinesias (PDC/PNKD) the attacks are of long duration and induced by variety of factors including coffee, tea, alcohol and fatigue but not by sudden movement [4].
• Pigmentary retinopathy of ALS/PDC in Kii [5].

Psychiatry related information on PDC

• Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia [6].
• Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder of Chamorro residents of Guam and the Mariana Islands, characterized by abundant neuron loss and tau neurofibrillary pathology similar to that observed in Alzheimer's disease (AD) [7].
• PHD including physical function (PF), role physical (RP), bodily pain (BP), general health (GH), and MHD including social function (SF), role mental/emotion function (RE), vitality (VT), perceptions of mental health (MH) were assessed [8].

High impact information on PDC

• SMCX bound H3K9me3 via its N-terminal PHD (plant homeodomain) finger, which may help coordinate H3K4 demethylation and H3K9 methylation in transcriptional repression [9].
• The gene product (PHF11) contains two PHD zinc fingers and probably regulates transcription [10].
• The murine gamma-herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression [11].
• Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can regulate p53 and histone acetylation in response to cellular stress and contains a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5-phosphate (PtdIns5P) [12].
• We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients [13].

Chemical compound and disease context of PDC

• These monoclonal antibodies, which are the first human monoclonal antibodies to pyruvate dehydrogenase complex generated from a patient with primary biliary cirrhosis, will be a valuable tool for studying the B-cell autoepitopes in PDC and the mechanism of autoantibody production in primary biliary cirrhosis [14].
• L-glutamate per se was gliotoxic only at concentrations much higher than the maximum reached with the potent EAAT substrate inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), and toxicity was lower [15].
• The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders [16].
• 4. MAM alters gene expression in SY5Y human neuroblastoma cells and, in the presence of DNA damage and reduced DNA repair, enhances glutamate-modulated expression of tau mRNA in rat primary neurons; the corresponding protein (TAU) is elevated in ALS/PDC and Alzheimer's disease [17].
• Thus in different cell types, isoform-specific patterns of PHD induction by hypoxia and estrogen alter both the relative abundance of the PHDs and their relative contribution to the regulation of HIF [18].

Biological context of PDC

• Our data show that the site of phosducin phosphorylation by GRK2 is different and independent from that previously reported for the cAMP-dependent protein kinase [19].
• Phosducin and its isoforms are widely distributed in body tissues where they may participate in signal transduction pathways [20].
• In this study, we identify new isoforms of the retinal phosducin and investigate the expression of the phosducin family, showing that an isoform, PhLP1, has sequence homology with Phd and Gbeta gamma binding capability, whereas two isoforms (phosducin-like orphan proteins, PhLOPs) share sequence homology with Phd but fail to bind Gbeta gamma [20].
• To explore a role for phosducin in regulated exocytosis, we have examined the distribution and putative function of phosducin-like protein (PhLP) in adrenal medullary chromaffin cells [21].
• Phosducin, which tightly binds betagamma-subunits of heterotrimeric G-proteins, has been conjectured to play a role in regulating second messenger signaling cascades, but to date its specific function has not been elucidated [22].

Anatomical context of PDC

• The full-length cDNA encoding the short splice variant of PhLP (PhLPs) was cloned from cultured chromaffin cells [21].
• In addition, transient expression of phosducin in COS-7 cells significantly inhibits G beta gamma-mediated phosphoinositide hydrolysis [23].
• Phosducin is a soluble photoreceptor phosphoprotein that probably modulates phototransduction in the retina and thus qualifies as a potential candidate gene for retinitis pigmentosa [24].
• However, the anti-bovine MEKA stained both rod and cone photoreceptor cells in the human retina [25].
• Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c+,CD123- myeloid DC (MDC)) or immunosuppressive T cell development (CD11c-,CD123+ plasmacytoid DC (PDC)) [26].

Associations of PDC with chemical compounds

• Accordingly, a glutathione S-transferase-fusion protein containing only the amino-terminal 105 amino acids of phosducin displayed G beta gamma binding ability [23].
• Calcium current inhibition after short-term exposure to norepinephrine was minimally altered by PDC or PDCL expression [27].
• The genotoxicant methylazoxymethanol (MAM) is a widely used developmental neurotoxin, and its glucoside is an etiological factor for western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS/PDC) [28].
• An immunoprecipitation assay also showed that the ciliate phosducin is indeed phosphorylated on a serine residue and exists in a phosphorylated form in darkness and that its dephosphorylation occurs in light [29].
• A nuclear preparation was obtained from the homogenate by sucrose gradient centrifugation, its purity was determined with a nuclear stain, and the presence and phosphorylation of phosducin was investigated as above [30].

Physical interactions of PDC

• This investigation concerns the expression of paired helical filaments, tau protein, ubiquitin, beta-amyloid protein, and synaptophysin in the hippocampus of patients with parkinsonism-dementia complex on Guam (PDC) and Alzheimer's disease [31].
• Here we have investigated whether phosducin interacts also with G-protein alpha subunits [32].

Enzymatic interactions of PDC

• These results, together with the finding that GRK2 may phosphorylate synuclein and phosducin in their acidic domains, indicate that some proteins with very acidic regions but without basic activation domains could serve as substrates for GRK2 [33].

Regulatory relationships of PDC

• Phosducin inhibits receptor phosphorylation by the beta-adrenergic receptor kinase in a PKA-regulated manner [34].

Other interactions of PDC

• Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2 [19].
• These results suggest an impaired maturation state of DC in PPMS patients, and a beneficial effect of IFN-beta favouring the survival of PDC and promoting a Th2 environment [1].
• The gene for human phosducin (PDC), a soluble protein that binds G-protein beta gamma dimers, maps to 1q25-q31.1 [35].
• CONCLUSIONS: Phosducin mutations are not a major cause of dominant or recessive RP, Leber congenital amaurosis, or cone-rod degeneration [36].
• Of note, within the HCV-PDC preparation, we noted a distinctly expanded DC subset that expressed some markers of MDC, but showed significantly lower HLA-DR and CD86 expression, suggesting an expansion of DC at an immature/intermediate stage of differentiation [37].

Analytical, diagnostic and therapeutic context of PDC

• Comparable results were observed when the GST-phosducin fusion proteins selectively sequestered Gbeta gammas from retinal extracts or when functional Gbeta gamma interactions were assessed using surface plasmon resonance technology [20].
• Assignment of the phosducin (PDC) gene to human chromosome 1q25-1q32.1 by somatic cell hybridization and in situ hybridization [24].
• Southern blot analysis revealed that the human MEKA gene has a single copy number [25].
• Phosducin was detected in the fractions by western blotting [30].
• Molecular cloning and characterization of the human phosducin-like protein (hPhLP) promoter [38].

References