dictyNews
Electronic Edition
Volume 34, number 7
February 26, 2010

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Abstracts
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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 [[log in to unmask]]
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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 [[log in to unmask]]
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[End dictyNews, volume 34, number 7]