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Biomedical subjects

G Gerisch

Publications and source records attributed to G Gerisch.

At least 145 records · Page 8Linked to original sources

PH oscillations in cell suspensions of Dictyostelium discoideum: their relation to cyclic-amp signals.

Cells of Dictyostelium discoideum known to release cyclic AMP (cAMP) rhythmically in the form of pulses, change with the same period of about 8 min the pH of their medium. The pH is used here as an indicator to investigate the effect of externally added cAMP pulses on the oscillations. Both a temporary increase in amplitude and a permanent phase shift can be induced. The phase-response curve indicates that the period can be increased and decreased by rhythmic stimulation with cAMP pulses.

Cyclic AMP↗

Implication of developmentally regulated Concanavalin A binding proteins of Dictyostelium in cell adhesion and cyclic AMP regulation.

Contact sites A and cyclic AMP phosphodiesterase are Concanavalin A binding membrane proteins. Both are characteristic for the aggregation phase of Dictyostelium discoideum. Extracellular cyclic AMP phosphodiesterase and an inhibitor of this enzyme can be recovered from the extracellular medium by binding to Concanavalin A-Sepharose.

3',5'-Cyclic-AMP Phosphodiesterases↗

Adenylyl cyclase and the control of cell differentiation in Dictyostelium dicoideum.

Adenylyl cyclase is part of a biochemical network that controls cell differentiation in Dictyostelium discoideum. At a certain stage of development the enzyme is rhythmically activated, with periods of about 8 min. These oscillations are superimposed upon an increase of the basal activity extending over a period of hours. The basal activity remains low in a mutant blocked at an early stage of development. In strain Ax-2 two periods of strongly increasing basal activity have been found: the first from 2 to 4 h after the end of the growth phase, the other beginning at about 8 h. Based on the periodic regulation of adenylyl cyclase, cyclic AMP is released into the extracellular space in the form of pulses. Application of cyclic-AMP pulses, but not its continuous influx, stimulates the increase of basal adenylyl cyclase activity. Two other constituents of the cyclic-AMP signal system cyclic-AMP receptors and cell-surface phosphodiesterase, are similarly controlled. The principal importance of positive feedback loops in a network controlling cell differentiation is discussed.

Adenylyl Cyclases↗

Extracellular cyclic-amp phosphodiesterase regulation in agar plate cultures of Dictyostelium discoideum.

Extracellular cyclic-AMP phosphodiesterase and the inhibitor of this enzyme is tested in agar plate cultures of two Dictyostelium discoideum wild-type strains and in a mutant which lacks the inhibitor. Under the conditions used, the phosphodiesterase inhibitor is formed in both wild-type strains either before or in an early stage of cell aggregation. During aggregation of one strain the phosphodiesterase activity is extremely low, excluding a necessary function of the enzyme in the aggregation process.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cell aggregation and sexual differentiation in pairs of aggregation-deficient mutants of Dictyostelium discoideum.

A diffusible aggregation-stimulating factor (ASF) is released from a series of aggregation-deficient mutants. Biochemical markers indicate that these ASF-donor mutants are blocked at a later step of cell differentiation than an ASF-requiring mutant. ASF is able to bridge the initial block of differentiation in the latter mutant, such that development proceeds up to aggregation and even further. ASF is most probably neither identical with cyclic-AMP phosphodiesterase nor with an inhibitor of this enzyme which both are released from donor strains. In certain combinations of aggregation-deficient mutants, macrocysts, the sexual stages of Dictyostelium, are formed. Also, motile giant cells believed to be zygotes are observed in these mutant combinations. The gamone known to be released from one mating type and to induce macrocysts in the other, is probably not identical with ASF since this factor is produced by mutants derived from either one of both mating types.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cell communication by periodic cyclic-AMP pulses.

At the surface of aggregating cells of the slime mould, Dictyostelium discoideum, two different sites interacting with extracellular cAMP are detectable: binding sites and cycl-nucleotide phosphodiesterase. Both sites are developmentally regulated. An adequate stimulus for the chemoreceptor system in D. discoideum is the change of cAMP concentration in time, rather than concentration per se: long-term binding of cAMP causes only short-term response. The system is, consequently, adapted to the recognition of pulses rather than to steady-state concentrations of cAMP. The ce,lls are, nevertheless, able to sense stationary spatial gradients and to respond to them by chemotactic orientation. The possibility is discussed that they do so by transforming spatial concentration changes into temporal ones, using extending pseudopods as sensors. The cAMP recognition system is part of a molecular network involved in the generation of spatio-temporal patterns of cellular activities. This system controls the periodic formation of chemotactic signals and their propagation from cell to cell. The phosphodiesterase limits the duration of the cAMP pulses and thus sharply separates the periods of signalling; the binding sites at the cell surface are supposed to be the chemoreceptors. The control of cellular activities via cAMP receptors can be studied with biochemical techniques with cell suspensions in which spatial inhomogeneities are suppressed by intense stirring, whereas the temporal aspect of the spatiotemporal pattern is preserved. Under these conditions it can be shown that the extracellular cAMP concentration changes periodically, and that the phase of the cellular oscillator can be shifted by external pulses of cAMP. It can also be shown that small cAMP pulses induce a high output of cAMP, which demonstrates signal amplification, a function necessary for a cellular relay system.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cyclic-AMP-controlled oscillations in suspended Dictyostelium cells: their relation to morphogenetic cell interactions.

Periodic spikes of decreased optical density were recorded in cell suspensions of Dictyostelium discoideum. Spike formation as well as changes in the redox state of cytochrome b are facultatively and independently coupled to an oscillating system which is under developmental control and presumably underlies signal transmission in aggregating cells. Cyclic AMP triggers a double response, the slow component resembling the spikes formed during spontaneous oscillations. The fast component shows characteristics of the chemotactic response to cyclic AMP. The receptor system is suggested to sense changes of cyclic AMP concentration in time. Cyclic AMP pulses interact with the oscillating system, resulting in phase shift or suppression of spike formation, and in the induction of oscillations in an early stage of development before the onset of spontaneous oscillations. Continuous flow application of cyclic AMP does not change frequency up to flow rates which extinguish oscillations.

Cell Aggregation↗

Short-term binding and hydrolysis of cyclic 3':5'-adenosine monophosphate by aggregating Dictyostelium cells.

Transient binding of cyclic AMP to aggregating cells of Dictyostelium discoideum was measured under cyclic GMP excess in order to inhibit cyclic AMP hydrolysis by cell-bound phosphodiesterase. Cyclic GMP extended the period of half-maximal cyclic AMP binding from less than 5 sec to 1-2 min. With the same time course as bound cyclic AMP was released from the cells, labeled 5'-AMP appeared in the medium. Specificity, kinetics, and developmental regulation suggest that the cyclic AMP-binding sites exposed in living cells are identical with receptor sites for the chemotactic response. The functioning of the cyclic AMP-receptor/phosphodiesterase system and its formal similarity with the synaptic acetylcholine-receptor/esterase system are discussed.

Binding Sites↗