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Biomedical subjects

P Schaap

Publications and source records attributed to P Schaap.

47 records · Page 3Linked to original sources
PubMed1988

Lithium respecifies cyclic AMP-induced cell-type specific gene expression in Dictyostelium.

We investigated the effect of LiCl on pattern formation and cAMP-regulated gene expression in Dictyostelium discoideum. In intact slugs, 5 mM LiCl induces an almost complete redifferentiation of prespore into prestalk cells. We found that LiCl acts by interfering with the transduction of extracellular cAMP to cell-type-specific gene expression; LiCl inhibits the induction of prespore-specific gene expression by cAMP, while it promotes the induction of prestalk-associated gene expression by cAMP. Our results indicate that two divergent pathways transduce the extracellular cAMP signal to, respectively, prestalk and prespore gene expression.

Chlorides↗
PubMed1988

Cell cycle phase in Dictyostelium discoideum is correlated with the expression of cyclic AMP production, detection, and degradation. Involvement of cyclic AMP signaling in cell sorting.

Cell cycle phase in Dictyostelium is correlated with a different preference for either spore or stalk differentiation. Cells which start development early in the cell cycle (E cells) exhibit a strong tendency to sort to the prestalk region of slugs, while late cell cycle cells (L cells) sort to the prespore region. We investigated the expression of the cAMP chemotactic system during development of synchronized E and L cells and found that E cells exhibit cAMP-binding activity, cell surface cAMP-phosphodiesterase (mPDE) activity, and the ability to relay cAMP signals at least 2 hr earlier and to higher levels than L cells. We hypothesize that E cells are prestalk sorters because they are the first to initiate aggregation centers and respond most effectively with chemotaxis and signal relay.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Localization of chemoattractant receptors on Dictyostelium discoideum cells during aggregation and down-regulation.

cAMP chemoattractant receptors on the surface of Dictyostelium discoideum cells are visualized by means of immunocytochemistry. Receptor antigen is virtually absent from growing cells and begins to accumulate after about 6 hr of starvation, concomitant with the increase in surface cAMP binding activity. In aggregating cells, the antigen is uniformly distributed over the cell surface. Persistent cAMP stimulation, which leads to down-regulation of cAMP binding activity, induces a striking rearrangement of receptor antigen into patches or internal vesicles. A similar patching of receptor antigen is observed during tight aggregate formation, when surface cAMP binding activity decreases. These observations indicate that receptor down-regulation involves receptor agglomeration and suggest that receptor down-regulation takes place in vivo, when tight aggregates are being formed.

Cell Aggregation↗
PubMed1986

Interactions between adenosine and oscillatory cAMP signaling regulate size and pattern in Dictyostelium.

We present evidence for the hypothesis that in multicellular structures of Dictyostelium, production of adenosine by hydrolysis of cAMP near the tip region prevents both generation of competing tips and differentiation of prespore cells near the tip, and thus establishes a "prestalk" region. We demonstrate that adenosine affects the immunological prespore specific staining pattern in slugs in a manner opposite to cAMP:cAMP induces an increase of prespore antigen; adenosine induces a decrease. When endogenous adenosine is removed from slugs, prespore vacuoles are synthesized throughout the prestalk region. Adenosine was found to inhibit the induction of prespore differentiation by cAMP in an apparently competitive manner. It was also found that adenosine specifically increased the amount of tissue controlled by one tip, probably by inhibiting generation of competing oscillators. Removing endogenous adenosine from slugs resulted in a decrease of tip dominance.

Adenosine↗
PubMed1986

Postaggregative differentiation induction by cyclic AMP in Dictyostelium: intracellular transduction pathway and requirement for additional stimuli.

Cyclic AMP induces postaggregative differentiation in aggregation competent cells of Dictyostelium by interacting with cell surface cAMP receptors. We investigated the transduction pathway of this response and additional requirements for the induction of postaggregative differentiation. Optimal induction of postaggregative gene expression requires that vegetative cells are first exposed to 2-4 hr of nanomolar cAMP pulses, and subsequently for 4-6 hr to steady-state cAMP concentrations in the micromolar range. Cyclic AMP pulses, which are endogenously produced before and during aggregation, induce full responsiveness to cAMP as a morphogen. The transduction pathway from the cell surface cAMP receptor to postaggregative gene expression may involve Ca2+ ions as intracellular messengers. A cAMP-induced increase in intracellular cAMP or cGMP levels is not involved in the transduction pathway.

Adenylyl Cyclases↗
PubMed1985

cAMP induces a transient elevation of cGMP levels during early culmination of Dictyostelium minutum.

Oscillatory cAMP signals very likely organize the cell movement which leads to fruiting body construction in Dictyostelium minutum [Schaap, P., Konijn, T.M. and Van Haastert, P.J.M.: Proc. Natl. Acad. Sci. USA 81, 2122-2126 (1984)]. Stimulation with cAMP induces a transient elevation of cGMP in cells at the early culmination stage, which peaks at 12-18 s. A half maximal cGMP response is induced by 10(-7) M cAMP and saturation of the response is reached at 10(-5) M cAMP. No cGMP accumulation was induced by stimulation of vegetative or aggregative cells of D. minutum by cAMP. Since the transient increase of cGMP is most likely involved in the transduction of chemotactic signals, our results indicate that cAMP signals organize fruiting body formation by inducing chemotaxis inside the aggregate.

Chemotaxis↗
PubMed1985

Induction of post-aggregative differentiation in Dictyostelium discoideum by cAMP. Evidence of involvement of the cell surface cAMP receptor.

Exogenous cAMP is known to induce post-aggregative differentiation in Dictyostelium discoideum under conditions that normal development is blocked. We have analysed the cyclic nucleotide specificity, the effect of modulation of the cAMP signal and the dose-response relationship of the induction of two independent markers of post-aggregative differentiation, i.e., a prespore cell-specific antigen detected by a monoclonal antibody, and the activity of glycogen phosphorylase. Our results confirm that high concentrations of cAMP (10(-6)-10(-3)M) are required for the induction of these markers. The cells are shown not to adapt to the cAMP signal. The cyclic nucleotide specificity of induction agrees with the specificity of the cell surface cAMP receptor, but is very dissimilar to the specificity of the intracellular cAMP-dependent protein kinase. It is thus unlikely that cAMP leaks into the cell and activates the cAMP-dependent protein kinase directly. Instead, the induction of post-aggregative differentiation by cAMP seems to be mediated by cell surface cAMP receptors.

Antibodies, Monoclonal↗
PubMed1984

The possible involvement of oscillatory cAMP signaling in multicellular morphogenesis of the cellular slime molds.

The involvement of pulsatile chemoattractant emission and signal relay in aggregation and multicellular morphogenesis of a variety of cellular slime mold species was investigated. The species differ from each other in the developmental stage when pulsatile signaling first becomes evident. In D. discoideum, D. mucoroides, and D. purpureum pulsatile signal emission starts in the preaggregative field. In D. vinaceo-fuscum, D. mexicanum, P. violaceum, and P. pallidum the aggregation centers shifts from continuous to pulsatile secretion of chemoattractant during the aggregation process. In D. minutum pulsatile signaling starts after the completion of aggregation and slightly before the onset of culmination. Tip formation is a consequence of continued attraction of amoebae inside the aggregate to the center of signal emission. The occurrence of pulsatile signaling at an early stage of development is correlated with the capacity of the tip (signaling center) to organize a relatively large number of cells into a single fruiting body. Several lines of evidence suggest that cAMP is probably involved in the coordination of morphogenetic movement in the multicellular stage of all investigated species.

Cell Membrane↗
PubMed1984

cAMP pulses coordinate morphogenetic movement during fruiting body formation of Dictyostelium minutum.

Aggregation in the primitive cellular slime mold Dictyostelium minutum proceeds by means of chemotaxis toward a continuously secreted folic acid analog [De Wit, R. J. W. & Konijn, T. M. (1983) Cell Differ. 12, 205-210]. The onset of culmination is marked by the appearance of concentric waves of cell movement on the aggregate surface. Culmination proceeds by the chemotactic attraction of amoebae to the center of wave propagation, which results in the accumulation of amoebae into a finger-like structure. Evidence is presented that the chemoattractant used during culmination is cAMP, which is secreted in pulses. The cells secrete cAMP themselves; cAMP receptors and phosphodiesterase activity appear on the cell surface just before the onset of culmination. Micromolar concentrations of externally applied cAMP induce disorientation of amoeboid movement at the onset of culmination. These observations are compatible with the hypothesis that the cAMP signaling system organizes multicellular development in both primitive and advanced cellular slime mold species. Advanced species such as Dictyostelium discoideum use this signaling system also in an earlier stage of development to organize the process of cell aggregation.

Journal Article↗
PubMed1983

The organisation of fruiting body formation in Dictyostelium minutum.

The process of culmination was investigated in three strains of the species Dictyostelium minutum. After aggregates have been formed a pulsatile signalling mechanism arises; the centre of signal emission becomes the apex of the developing fruiting structure. In the late aggregate, all cells differentiate into prespore cells. Cells that have reached the apex of the culminating cells mass redifferentiate into stalk cells. In two of the three D. minutum strains, interruption of regular stalk formation, more or less random formation of stalk cells and the synthesis of stalk supporting material from cell debris often takes place. The formation of multiple apices on aggregates and early fruiting structures is characteristic for these two strains. Within the species D. minutum, the exhibition of a marked pulsatile signalling mechanism is correlated with a capacity to form a regularly shaped stalk and to organize relatively large cell masses. The possible function of pulsatile signalling in the culmination process is discussed.

Cell Differentiation↗