Biomedical subjects

M J Peacey

Publications and source records attributed to M J Peacey.

4 recordsLinked to original sources

PubMed1988

Plasma membrane proton pump inhibition and stalk cell differentiation in Dictyostelium discoideum.

The choice of the stalk cell differentiation pathway in Dictyostelium is promoted by an endogenous substance, DIF-1, which is 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone. It is also favoured by weak acids and two inhibitors of the plasma membrane proton pumps of fungi and plants, diethylstilbestrol (DES) and zearalenone, and antagonised by ammonia and other weak bases, which promote spore differentiation. These observations led to the proposal that the choice of differentiation pathway is regulated by intracellular pH. They also prompted the conjecture that DIF-1 itself is a plasma membrane proton pump inhibitor. We report here experiments showing that DIF-1 is not a plasma membrane proton pump inhibitor. We demonstrate that diethylstilbestrol and zearalenone do inhibit the plasma membrane proton pump of Dictyostelium and we show that there is an excellent qualitative and quantitative correlation between the inhibitory activity of these agents, and of a number of other substances, and their ability to divert differentiation from the spore to the stalk pathway. We conclude that inhibition of the plasma membrane proton pump does shift the choice of differentiation pathway in Dictyostelium towards the stalk pathway, but that DIF does not act by this route, and we propose a model for the actions of DIF and plasma membrane proton pump inhibitors in which the differentiation pathway is controlled by the pH of intracellular vesicles rather than by intracellular pH itself. The model invokes a DIF- and proton-activated vesicular chloride channel whose opening permits acidification of the vesicles and lowers cytosolic Ca++ concentration.

Adenosine Triphosphatases↗

PubMed1981

Cell patterning in Dictyostelium.

We summarize studies on stalk and spore cell formation in D. discoideum cell monolayers, aimed at revealing factors involved in controlling the prestalk:prespore pattern in this organism. We propose that there are no cell interactions dependent on cell contact per se. Formation of mature stalk cells from isolated amoebae incubated in a buffered salts medium requires only cyclic AMP and a lipid-like factor (DIF) released by cells developing at high density. In addition, a variety of sporogenous mutants can form spores rapidly and efficiently when incubated at low density in tissue culture dishes containing a similar cyclic AMP and salts medium. In some cases spore formation is improved by the addition of one or other of a variety of protective agents such as bovine serum albumin. Wild-type amoebae at low density form prespore cells under the same conditions. We present some evidence that DIF is the activator of prestalk cell formation in a two-component patterning mechanism of the kind proposed by Wolpert et al. (Symp. Soc. exp. Biol. 25, 391-415 (1971)) and Gierer & Meinhardt (Kybernetik 12, 30-39 (1972)). We also provide data indicating that the role of inhibitor is played by ammonia, an idea first mooted by Sussman & Schindler (Differentiation 10, 1-5 (1978)).

Cell Adhesion↗

PubMed1976

Signal emission and signal propagation during early aggregation in Dictyostelium discoideum.

Waves of chemotactic movement during the early phase of aggregation in Dictyostelium discoideum are of 2 kinds, concentric waves produced by cells that emit cyclic AMP signals spontaneously, and spirals generated by excitations relayed continuously around loops of excitable cells. The period of a spiral wave is the time taken for the excitation to make one complete circuit of the pacemaker loop. We have compared signal emission from the 2 types of source in time-lapse films made at a variety of temperatures. Our results show that spiral waves have a characteristic period length throughout most if not all of the early phase of aggregation, and that the period of concentric waves is generally longer and more variable. Temperature has a pronounced effect on period length and a lesser effect on propagation velocity. We find that each individual wave is propagated at constant velocity over distances of 1-2 cm but that the velocity of successive waves declines. This decline probably reflects some cumulative effect of the chemotactic excitations on the excitable properties of the aggregating cells.

Analysis of Variance↗

PubMedDate not supplied

Intracellular pH and the control of cell differentiation in Dictyostelium discoideum.

During development in the cellular slime mould Dictyostelium discoideum starved amoebae aggregate to form multicellular structures that display a simple antero-posterior pattern: prestalk cells occupy the front 20% of the aggregate, and prespore cells occupy the remainder. We have attempted to elucidate the nature of the mechanism regulating the proportions of the two cell types by examining the factors that influence the pathway of differentiation of amoebae in vitro. Amoebae of D. discoideum strain V12 M2 form stalk cells efficiently in appropriate conditions and 'sporogenous' derivatives produce spores as well as stalk cells. Mature spores are formed in a medium containing only cyclic AMP and salts, whereas formation of stalk cells requires, in addition, a low molecular weight hydrophobic factor (DIF). Recent observations have led us to propose that DIF is a morphogen responsible for activating stalk cell differentiation. Here we present evidence that ammonia is a second morphogen, that acts antagonistically to DIF, and that the choice of differentiation pathway is mediated by intracellular pH.

Ammonia↗