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First published online 28 January 2009
doi: 10.1242/dev.032607
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Center for Molecular Genetics, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
* Author for correspondence (e-mail: wloomis{at}ucsd.edu)
Accepted 4 January 2009
Encapsulation of prespore cells of Dictyostelium discoideum is
controlled by several intercellular signals to ensure appropriate timing
during fruiting body formation. Acyl-CoA-binding protein, AcbA, is secreted by
prespore cells and processed by the prestalk protease TagC to form the 34
amino acid peptide SDF-2 that triggers rapid encapsulation. AcbA is secreted
when
-aminobutyric acid (GABA) is released from prespore cells and
binds to GrlE, a G protein-coupled receptor (GPCR). Analysis of SDF-2
production in mutant strains lacking G
subunits and GPCRs, either as
pure populations or when mixed with other mutant strains, uncovered the
non-cell-autonomous roles of GrlA, G
4 and G
7. We found that
G
7 is essential for the response to GABA and is likely to be coupled to
GrlE. GrlA-null and G
4-null cells respond
normally to GABA but fail to secrete it. We found that they are necessary for
the response to a small hydrophobic molecule, SDF-3, which is released late in
culmination. Pharmacological inhibition of steroidogenesis during development
blocked the production of SDF-3. Moreover, the response to SDF-3 could be
blocked by the steroid antagonist mifepristone, whereas hydrocortisone and
other steroids mimicked the effects of SDF-3 when added in the nanomolar
range. It appears that SDF-3 is a steroid that elicits rapid release of GABA
by acting through the GPCR GrlA, coupled to G protein containing the G
4
subunit. SDF-3 is at the head of the cascade that amplifies the signal for
encapsulation to ensure the rapid, synchronous formation of spores.
Key words: Steroids, SDF-2, SDF-3, G protein-coupled receptor, GrlA
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