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How
can a group of undifferentiated cells break symmetry and become
different cell types? If the cells are at different phases of
the cell cycle a signal can tell them to look at what phase they
happen to be in and this will determine their initial fate.
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In wild-type, prestalk cells
originate from cells in S phase or early G2 at starvation, while
in rtoA they originate randomly from cells in any phase
of the cell cycle. |
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Wild-type |
rtoA
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I n Dictyostelium, initial cell type choice is correlated with
the cell-cycle phase of the cell at the time of starvation. For
each pair of sister cells which happen to be in S or early G2 phase (Dictyostelium
does not have a G1 phase) when they starve, one sister differentiates
into a prestalk cell while the other sister becomes a null cell (a cell
that does not express either a characteristic prestalk or a prespore antigen).
Cells starved in late G2 or M phase similarly differentiate into either
a prespore or a null cell. We have isolated a mutant, ratioA (rtoA),
with a defect in this mechanism that results in an abnormally high percentage
of prestalk cells. The cell cycle is normal in rtoA. In the wild
type, prestalk cells differentiate from those cells in S or early G2 phase
at starvation and prespore cells from cells in late G2 or M phase at starvation.
In rtoA mutants, both prestalk and prespore cells originate randomly
from cells in any phase of the cell cycle at starvation. Through
further work we have found that rtoA cells have a defect
in the fusion of endocytic vesicles. They also have a decreased exocytosis
rate, a decreased pH of endocytic/exocytic vesicles, and an increased
average cytosolic pH. Our data indicate that the serine-rich domain of
RtoA can mediate membrane fusion and that RtoA can increase the rate of
vesicle fusion during processing of endoctyic vesicles. We hypothesize
that RtoA modulates initial cell type choice by linking vegetative cell
physiology to the cell cycle.
Key Papers
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RtoA
links initial cell type choice to the cell cycle in Dictyostelium.
Wood SA, Ammann RR, Brock DA, Li L, Spann T, Gomer RH. Development
1996 122:3677-85
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A
protein containing a serine-rich domain with vesicle fusing properties
mediates cell cycle-dependent cytosolic pH regulation.
Brazill DT, Caprette DR, Myler HA, Hatton RD, Ammann RR, Lindsey
DF, Brock DA, Gomer RH. J Biol Chem 2000 275:19231-40
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The phase of the cell
cycle at starvation influences the level of cellular Ca2+
and, thereby post-aggregative cell fate in Dictyostelium discoideum.
Azhar, M., Kennady, P.K., Pande, G., Espiritu, M., Holloman, W., Brazill,
D., Gomer, R.H., and Nanjundiah, V. Int. J. Dev. Bio.
2001 44, 405-414
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Mutagenesis
and gene identification in Dictyostelium by shotgun antisense.
Spann TP, Brock DA, Lindsey DF, Wood SA, Gomer RH. Proc
Natl Acad Sci U S A 1996 93:5003-7
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Gene
identification by shotgun antisense. Gomer RH.
Methods 1999 18:311-5
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