An F-Box/WD40 repeat-containing protein important for Dictyostelium cell-type proportioning, slug behaviour, and culmination.

FbxA is a novel member of a family of proteins that contain an F-box and WD40 repeats and that target specific proteins for degradation via proteasomes. In fruiting bodies formed from cells where the fbxA gene is disrupted (fbxA(-) cells), the spore mass fails to fully ascend the stalk. In addition, fbxA(-) slugs continue to migrate under environmental conditions where the parental strain immediately forms fruiting bodies. Consistent with this latter behaviour, the development of fbxA(-) cells is hypersensitive to ammonia, the signaling molecule that regulates the transition from the slug stage to terminal differentiation. The slug comprises an anterior prestalk region and a posterior prespore region and the fbxA mRNA is highly enriched in the prestalk cells. The prestalk zone of the slug is further subdivided into an anterior pstA region and a posterior pstO region. In fbxA(-) slugs the pstO region is reduced in size and the prespore region is proportionately expanded. Our results indicate that FbxA is part of a regulatory pathway that controls cell fate decisions and spatial patterning via regulated protein degradation.

[1]  R. Kessin,et al.  Dictyostelium amoebae lacking an F-box protein form spores rather than stalk in chimeras with wild type , 2000 .

[2]  T. Maniatis,et al.  A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. , 1999, Genes & development.

[3]  Zhijian J. Chen,et al.  Signal-induced ubiquitination of IκBα by the F-box protein Slimb/β-TrCP , 1999 .

[4]  Stephen J. Elledge,et al.  The SCFβ-TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro , 1999 .

[5]  M. Mann,et al.  Identification of the receptor component of the IκBα–ubiquitin ligase , 1998, Nature.

[6]  K. Zhou,et al.  A novel, putative MEK kinase controls developmental timing and spatial patterning in Dictyostelium and is regulated by ubiquitin-mediated protein degradation. , 1998, Genes & development.

[7]  B. Mykytka,et al.  The histidine kinase dhkC regulates the choice between migrating slugs and terminal differentiation in Dictyostelium discoideum. , 1998, Developmental biology.

[8]  J. Sternfeld The anterior-like cells in Dictyostelium are required for the elevation of the spores during culmination , 1998, Development Genes and Evolution.

[9]  R. Kessin,et al.  A Novel Component Involved in Ubiquitination Is Required for Development of Dictyostelium discoideum * , 1998, The Journal of Biological Chemistry.

[10]  M. Tyers,et al.  Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis. , 1998, Trends in genetics : TIG.

[11]  D. Thomas,et al.  A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. , 1998, Molecular cell.

[12]  G. Struhl,et al.  Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb , 1998, Nature.

[13]  G. Wu,et al.  sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins. , 1997, Genes & development.

[14]  R. Simon,et al.  Dual role for fimbriata in regulating floral homeotic genes and cell division in Antirrhinum , 1997, The EMBO journal.

[15]  R. Firtel,et al.  A ubiquitin-conjugating enzyme is essential for developmental transitions in Dictyostelium. , 1997, Molecular biology of the cell.

[16]  J. Williams,et al.  cudA: a Dictyostelium gene with pleiotropic effects on cellular differentiation and slug behaviour. , 1997, Development.

[17]  Stephen J. Elledge,et al.  SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box , 1996, Cell.

[18]  A. Kuspa,et al.  Ordered yeast artificial chromosome clones representing the Dictyostelium discoideum genome. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Blangero,et al.  Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[20]  Jeffrey G. Williams,et al.  Evidence for positional differentiation of prestalk cells and for a morphogenetic gradient in dictyostelium , 1995, Cell.

[21]  W. Loomis,et al.  Whole-mount in situ hybridization of cell-type-specific mRNAs in Dictyostelium. , 1995, Developmental biology.

[22]  R. Simon,et al.  Parallels between UNUSUAL FLORAL ORGANS and FIMBRIATA, genes controlling flower development in Arabidopsis and Antirrhinum. , 1995, The Plant cell.

[23]  E. Bier,et al.  Double-label in situ hybridization using biotin and digoxigenin-tagged RNA probes. , 1994, BioTechniques.

[24]  Raman Nambudripad,et al.  The ancient regulatory-protein family of WD-repeat proteins , 1994, Nature.

[25]  Florian Siegert,et al.  Patterns of cell movement within the Dictyostelium slug revealed by cell type-specific, surface labeling of living cells , 1994, Cell.

[26]  J. Gross,et al.  Ammonia hypersensitivity of slugger mutants of D. discoideum. , 1994, Journal of cell science.

[27]  K. Sutoh A transformation vector for dictyostelium discoideum with a new selectable marker bsr. , 1993, Plasmid.

[28]  J. Williams,et al.  Two distinct populations of prestalk cells within the tip of the migratory Dictyostelium slug with differing fates at culmination. , 1993, Development.

[29]  S. Taylor,et al.  DdPK3, which plays essential roles during Dictyostelium development, encodes the catalytic subunit of cAMP-dependent protein kinase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Kuspa,et al.  Tagging developmental genes in Dictyostelium by restriction enzyme-mediated integration of plasmid DNA. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Williams,et al.  Culmination in dictyostelium is regulated by the cAMP-dependent protein kinase , 1992, Cell.

[32]  Jeffrey G. Williams,et al.  Positively and negatively acting signals regulating stalk cell and anterior-like cell differentiation in dictyostelium , 1991, Cell.

[33]  J. Williams,et al.  An analysis of culmination in Dictyostelium using prestalk and stalk-specific cell autonomous markers. , 1991, Development.

[34]  J. Faix,et al.  Constitutive overexpression of the contact site A glycoprotein enables growth‐phase cells of Dictyostelium discoideum to aggregate. , 1990, The EMBO journal.

[35]  T. Dingermann,et al.  Optimization and in situ detection of Escherichia coli beta-galactosidase gene expression in Dictyostelium discoideum. , 1989, Gene.

[36]  J. Williams,et al.  Structural characterization of Dictyostelium discoideum prespore-specific gene D19 and of its product, cell surface glycoprotein PsA , 1988, Molecular and cellular biology.

[37]  H. Lodish,et al.  Developmental regulation of Dictyostelium discoideum actin gene fusions carried on low-copy and high-copy transformation vectors , 1986, Molecular and cellular biology.

[38]  R. Firtel,et al.  DNA-mediated transformation in Dictyostelium discoideum: regulated expression of an actin gene fusion , 1984, Molecular and cellular biology.

[39]  K. Williams,et al.  Analysis of proportion regulation in slugs of Dictyostelium discoideum using a monoclonal antibody and a FACS-IV. , 1983, Experimental cell research.

[40]  P. Newell,et al.  Genetic Analysis of the Slug Stage of Dictyostelium discoideum , 1982 .

[41]  K. Williams,et al.  Evidence for tip control of the 'slug/fruit' switch in slugs of Dictyostelium discoideum. , 1980, Journal of embryology and experimental morphology.

[42]  M. Sussman,et al.  Ammonia determines the choice of morphogenetic pathways in Dictyostelium discoideum. , 1977, Journal of molecular biology.

[43]  I. Takeuchi,et al.  Quantitative studies on cell differentiation during morphogenesis of the cellular slime mold Dictyostelium discoideum. , 1976, Developmental biology.

[44]  J. Ashworth,et al.  Growth of myxameobae of the cellular slime mould Dictyostelium discoideum in axenic culture. , 1970, The Biochemical journal.

[45]  D. Francis SOME STUDIES ON PHOTOTAXIS OF DICTYOSTELIUM. , 1964, Journal of cellular and comparative physiology.

[46]  R. Kessin,et al.  Dictyostelium amoebae lacking an F-box protein form spores rather than stalk in chimeras with wild type. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  S. Elledge,et al.  The SCF–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkBa and b-catenin and stimulates IkBa ubiquitination in vitro , 1999 .

[48]  K. Anderson,et al.  Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. , 1995, Annual review of genetics.