title: A divergent multi-domain cyclophilin is highly conserved between parasitic and free-living nematode species and is important in larval muscle development.
abstract: A divergent multi-domain cyclophilin from the filarial nematodes Brugia malayi, Onchocerca volvulus and Dirofilaria immitis has a highly conserved orthologue in the free-living nematodes Caenorhabditis elegans and C. briggsae. Cyclophilins are the receptors for the immunosuppressive and anti-parasitic agent cyclosporin A and additionally these ubiquitously expressed proteins have protein folding capabilities, and exhibit proline isomerase activity. These divergent nematode cyclophilins (CYP-4 isoforms) are three domain proteins, which share 63-88% identity and have highly conserved differences present in their functionally important cyclosporin A binding and proline isomerase domains. This unusual class of nematode cyclophilins has been studied in the model nematode C. elegans, revealing a unique temporal and spatial expression pattern. The cyp-4 transcript is most abundantly expressed in the early larval stages and is expressed exclusively in the body-wall striated muscle cells. An important functional role was established for this divergent enzyme, as specific double-stranded RNA interference experiments resulted in progeny with a phenotypically lumpy appearance. This morphological defect was predominantly expressed in the early larval stages and is consistent with an effect on body-wall muscle cell development. This study has established that this highly conserved family of nematode cyclophilins has a tissue-specific, functional role in early larval development and supports the use of C. elegans as a model for the study of orthologues in the experimentally less amenable parasitic nematodes.
authors.affiliation: Wellcome Unit of Molecular Parasitology, Anderson College, University of Glasgow, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Page
authors.forename: A D
authors.initials: AD
authors.lastname: Winter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D017124:Conserved Sequence; D018076:DNA, Complementary; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D017930:Genes, Reporter; D006801:Humans; D007527:Isoenzymes; D007814:Larva / Q000201:enzymology; D008969:Molecular Sequence Data; D024510:Muscle Development; D009348:Nematoda / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; D012330:RNA, Double-Stranded; D019696:Peptidylprolyl Isomerase