Key result
Adenylyl cyclase cAMP synthesis remains essential for Dictyostelium spore differentiation despite constitutively high PKA activity.
Why the study?
The role of adenylyl cyclases acaA and acrA in Dictyostelium development and spore differentiation under constitutive PKA activity was unclear.
Synthesis of cAMP is required for spore differentiation in Dictyostelium even when PKA activity is constitutively high.
No immediate clinical implications; leaves open whether adenylyl cyclase requirements beyond PKA generalize to mammalian differentiation.
It has been suggested that all intracellular signaling by cAMP during development of Dictyostelium is mediated by the cAMP-dependent protein kinase, PKA, since cells carrying null mutations in the acaA gene that encodes adenylyl cyclase can develop so as to form fruiting bodies under some conditions if PKA is made constitutive by overexpressing the catalytic subunit. However, a second adenylyl cyclase encoded by acrA has recently been found that functions in a cell autonomous fashion during late development. We have found that expression of a modified acaA gene rescues acrA- mutant cells indicating that the only role played by ACR is to produce cAMP. To determine whether cells lacking both adenylyl cyclase genes can develop when PKA is constitutive we disrupted acrA in a acaA- PKA-C(over) strain. When developed at high cell densities, acrA- acaA- PKA-C(over) cells form mounds, express cell type-specific genes at reduced levels and secrete cellulose coats but do not form fruiting bodies or significant numbers of viable spores. Thus, it appears that synthesis of cAMP is required for spore differentiation in Dictyostelium even if PKA activity is high.
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Anjard et al. (2001) studied Dictyostelium development. Disruption of acrA and acaA genes was evaluated on Spore differentiation and fruiting body formation. Synthesis of cAMP by adenylyl cyclases is required for spore differentiation in Dictyostelium even when PKA activity is constitutively high.
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