dictyNews Electronic Edition Volume 34, number 7 February 26, 2010 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. Follow dictyBase on twitter: http://twitter.com/dictybase ========= Abstracts ========= BTG Interacts with Retinoblastoma to Control Cell Fate in Dictyostelium Daniele Conte, Harry K. MacWilliams & Adriano Ceccarelli PLoS ONE, in press Background In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering of differentation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. Methodology/principal findings Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell) fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. Conclusions/Significance While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the evolution of multicellularity. Submitted by Adriano Ceccarelli [adriano.ceccarelli@unito.it] -------------------------------------------------------------------------------- MidA is a putative mitochondrial methyltransferase required for mitochondrial complex I function Sergio Carilla-Latorre1; M. Esther Gallardo1,4; Sarah J. Annesley2; Javier Calvo-Garrido1; Osvaldo Graña3; Sandra L. Accari2, Paige K. Smith2, Alfonso Valencia3; Rafael Garesse1,4; Paul R. Fisher2 and Ricardo Escalante1 1. Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM). Arturo Duperier 4. 28029 Madrid. Spain. 2. Department of Microbiology, La Trobe University, Melbourne, Victoria 3086. Australia. 3. O. G., Bioinformatics Unit, Structural Biology and Biocomputing Program. A. V., Structural Computational Biology Group, Structural Biology and Biocomputing Program.Centro Nacional de Investigaciones Oncológicas. C/ Melchor Fernández Almagro, 3, 28029 Madrid. Spain. 4. CIBERER, ISCIII. Madrid. Spain. Journal of Cell Science, in press Dictyostelium and human MidA (DdMidA and hMidA) are homologous proteins that belong to a family of proteins of unknown function called DUF185. We have found by a yeast-two hybrid screening and subsequent validation by pull-down that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knock down of hMidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain that was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in Dictyostelium midA- mutant causes a complex phenotypic outcome including phototaxis and thermotaxis defects. We have found that these aspects of the phenotype are mediated by a chronic activation of AMPK revealing a possible role of AMPK signaling in complex I cytopathology. Submitted by Ricardo Escalante [rescalante@iib.uam.es] ============================================================== [End dictyNews, volume 34, number 7]