title: The thyroxine inactivating gene, type III deiodinase, suppresses multiple signaling centers in Dictyostelium discoideum.
abstract: Thyroxine deiodinases, the enzymes that regulate thyroxine metabolism, are essential for vertebrate growth and development. In the genome of Dictyostelium discoideum, a single intronless gene (dio3) encoding type III thyroxine 5' deiodinase is present. The amino acid sequence of D. discoideum Dio3 shares 37% identity with human T4 deiodinase and is a member of the thioredoxin reductase superfamily. dio3 is expressed throughout growth and development and by generating a knockout of dio3, we have examined the role of thyroxine 5' deiodinase in D. discoideum. dio3(-) had multiple defects that affected growth, timing of development, aggregate size, cell streaming, and cell-type differentiation. A prominent phenotype of dio3(-) was the breaking of late aggregates into small signaling centers, each forming a fruiting body of its own. cAMP levels, its relay, photo- and chemo-taxis were also defective in dio3(-). Quantitative RT-PCR analyses suggested that expression levels of genes encoding adenylyl cyclase A (acaA), cAMP-receptor A (carA) and cAMP-phosphodiesterases were reduced. There was a significant reduction in the expression of CadA and CsaA, which are involved in cell-cell adhesion. The dio3(-) slugs had prestalk identity, with pronounced prestalk marker ecmA expression. Thus, Dio3 seems to have roles in mediating cAMP synthesis/relay, cell-cell adhesion and slug patterning. The phenotype of dio3(-) suggests that Dio3 may prevent the formation of multiple signaling centers during D. discoideum development. This is the first report of a gene involved in thyroxine metabolism that is also involved in growth and development in a lower eukaryote.
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600036, India.
authors.forename: Shashi Prakash
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600036, India.
authors.forename: Ranjani
authors.initials: R
authors.lastname: Dhakshinamoorthy
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600036, India.
authors.forename: Pundrik
authors.initials: P
authors.lastname: Jaiswal
authors.affiliation: Institute for Biology - Microbiology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Institute for Biology - Microbiology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Thewes
authors.affiliation: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600036, India. Electronic address: rbaskar@iitm.ac.in.
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Baskar
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D004023:Dictyostelium / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D011953:Receptors, Cyclic AMP; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D000251:Adenosine Triphosphatases; C059771:cadmium translocating ATPase; D000262:Adenylyl Cyclases
keywords: Dictyostelium; Signaling; Thyroxine 5′ deiodinase; dio3