Disease relevance of daf-21

• Under heat stress conditions, however, daf-21 mRNA was not only detected in germ cells, but also apparently expressed all over the body [1].

High impact information on daf-21

• Caenorhabditis elegans daf-11 and daf-21 mutants share defects in specific chemosensory responses mediated by several classes of sensory neurons, indicating that these two genes have closely related functions in an assortment of chemosensory pathways [2].
• We show that the viable chemosensory-deficient daf-21 mutation is an unusual allele resulting from a single amino acid substitution and that the daf-21 null phenotype is early larval lethality [2].
• These results demonstrate that cGMP is a prominent second messenger in C. elegans chemosensory transduction and suggest a previously unknown role for Hsp90 in regulating cGMP levels [2].
• To examine this possibility, here we have used double-stranded RNA interference (RNAi) against PA28 in Caenorhabditis elegans mutants of daf-21, which encodes Hsp90 [3].
• In this review, the relationship between temperature and development in filarial nematodes and in the free-living species Caenorhabditis elegans is summarised, with a focus on the role of heat shock factor and heat shock protein 90 in the nematode life cycle [4].

Biological context of daf-21

• Cell cycle control by daf-21/Hsp90 at the first meiotic prophase/metaphase boundary during oogenesis in Caenorhabditis elegans [5].
• To phenocopy daf-21 mutations, we impaired the daf-21 function by RNA interference (RNAi), and found that oocytes skipped the diakinesis arrest and displayed a defective diakinesis arrest, which led to the production of endomitotic oocytes with polyploid chromosomes (Emo phenotype) [5].
• These findings provide new insights into the nature of unusual N-terminal nucleotide-binding fold of Hsp90 and suggest that target-related drug resistance is unlikely to emerge in patients receiving GA-like chemotherapeutic agents [6].
• However, exposure of worms to GA produced no discernable phenotypes, although the amino acid sequence of worm Hsp90 is 85% homologous to that of human Hsp90 [6].

Anatomical context of daf-21

• Under normal conditions, daf-21 mRNA is characteristically distributed in postembryonic germ cells derived from Z2 and Z3 cells in both hermaphrodites and males [1].
• Consistent with this observation, we found that solid phase-immobilized GA failed to bind worm Hsp90 from worm protein extracts or when translated in a rabbit reticulocyte lysate system [6].

Associations of daf-21 with chemical compounds

• Despite its unusual GA resistance, worm Hsp90 appeared fully functional when expressed in a vertebrate background [6].
• Crystal structures of the N-terminal region of yeast and human Hsp90 have revealed that these compounds interact with the chaperone in a Bergerat-type adenine nucleotide-binding fold shared throughout the gyrase, Hsp90, histidine kinase mutL (GHKL) superfamily of adenosine triphosphatases [6].

Analytical, diagnostic and therapeutic context of daf-21

• The spatial and temporal distribution of the antigen (DAF-21) was analyzed in C. elegans, and the localization of daf-21 mRNA, as detected by in situ hybridization, agreed with that detected by the monoclonal antibody [1].
• Thus, Hsp90 or some of its client proteins may provide novel targets for the chemotherapy of filarial infection [7].

References