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Biomedical subjects

G Gerisch

Publications and source records attributed to G Gerisch.

At least 127 records · Page 7Linked to original sources
PubMed1981

Folate deaminase and cyclic AMP phosphodiesterase in Dictyostelium discoideum: their regulation by extracellular cyclic AMP and folic acid.

Cyclic AMP and folic acid act as chemotactic factors in Dictyostelium discoideum. Both agents, when applied extracellularly, also control cell development from the growth stage to the acquisition of aggregation competence. Cyclic AMP phosphodiesterase and folate deaminase are extracellular enzymes whose activity is regulated during early differentiation of D. discoideum cells. The two enzymes help control the extracellular levels of cyclic AMP and folic acid. The substrates cyclic AMP and folic acid each increase the extracellular activity of folate deaminase as well as phosphodiesterase. The specificity of extracellular phosphodiesterase regulation by cyclic AMP indicates that the effect is mediated by specific cyclic AMP receptors rather than the catalytic site of cell surface phosphodiesterase. To some extent cyclic AMP and folic acid are interchangeable with respect to regulating differentiation and enhancing enzymatic inactivation of intercellular signals. Thus the two extracellular signals may share a common cellular pathway of signal transduction. The regulation of folate deaminase and phosphodiesterase by folic acid does not always parallel the folic acid effects on development. Pulses of folic acid stimulate development of aggregation competence, whereas a continuous flux inhibits. In contrast, either continuous flux or pulses of folic acid increase the deaminase and phosphodiesterase activities.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Chemotactic reorientation of granulocytes stimulated with micropipettes containing fMet-Leu-Phe.

Human granulocytes were stimulated by means of a micropipette, with an orifice of about 0.2 micrometer in diameter, which contained fMet-Leu-Phe at a concentration of 10(-5) M. The cells were reorientated by extending lamellipodia towards the source of the attractant, often within less than 10 s. Any part of the granulocyte, from the front to the tip of the tail, could be stimulated to produce new lamellipodia. Usually, but not always, this response occurred at the side of the cell nearest to the micropipette. Cells stimulated from behind responded in one of the following ways: (1) Cells that maintained their polarity extended new lamellipodia at one side of the leading front and reorientated by moving in a U-turn towards the micropipette. Occasionally, the leading front was split because one part of the front tried to make a left-hand and the other a right-hand turn. (2) Formation of lamellipodia at the leading front was arrested and new lamellipodia were formed at the tail instead, indicating reversal of polarity. The result was an immediate change in the direction of locomotion by about 180 degrees. (3) A combination of the first 2 forms of behaviour was observed occasionally. Transiently, lamellipodia were extended from cell surface areas both close to and distant from the micropipette. These observations show that parts of a cell can respond independently to chemotactic gradients by extending lamellipodia towards the source of the attractant. The phenomenon can easily be explained by assuming that a temporal change of attractant concentration is recognized.

Chemotactic Factors↗
PubMed1980

Protein-bound mono(ADP-ribose) residues in differentiating cells of Dictyostelium discoideum.

Changes in protein-bound mono(ADP-ribose) residues during development of Dictyostelium discoideum were determined. NAD(H) levels and the amounts of the NH2OH resistant and sensitive subfractions of mono(ADPR) were found not to be different between exponentially growing and aggregation-competent cells in which mitosis had ceased. Divergent changes occurred at the differentiation stages following aggregation as indicated by an increase in the ratio of these subfractions from approx. 1 during the growth plase and aggregation competent stage to 2 in the grex, a stage which follows cell aggregation. The fraction of NH2OH sensitive conjugates closely followed the changes in total cellular protein, while the NH2OH resistant ADPR protein conjugates, when based on protein, increased during the stages following aggregation. NAD(H) and NADP(H) levels per unit DNA decreased significantly during this period. The mono(ADPR) to DNA ratio in D. discoideum is comparable to that in proliferating Physarum polycephalum and to non-proliferating adult rat liver. The total amount of mono(ADPR) residues per nucleus is, however, approximately 70-fold higher in the liver, indicating that the quantity of mono(ADPR) residues is more closely related to the size of the eukaryotic genome than to cell proliferation.

Adenosine Diphosphate Ribose↗
PubMed1979

Cell surface protein kinases in Dictyostelium: are they artifacts?

Evidence for cell surface protein kinases as possible regulatory factors of cell interaction in Dictyostelium discoideum was examined by incubating intact cells with gamma 32P-ATP in the presence and absence of histone. No significant incorporation of 32P was detected in the absence of histone. In its presence strong phosphorylation not only of the histone but also of endogenous proteins was obtained. This was due to the fact that histone made the cell membranes permeable for substrates and proteinkinases. Histone also preserved protein kinase activities which were otherwise lost during homogenization. The total protein kinase activity in histone treated cells was 5 fold higher than in sonicated cells.

Adenosine Triphosphate↗
PubMed1979

A transient rise in cyclic AMP levels following chemotactic stimulation of neutrophil granulocytes.

A short transient rise of cyclic AMP is observed within 1 minute after primary stimulation of neutrophils with chemotactic serum peptides containing classical anaphylatoxin (CAT). A second administration of these peptides after two minutes failed to produce a second peak of cAMP. Human serum albumin (HSA) which has chemokinetic but no chemotactic activities did not change cAMP levels. There was no significant change in cGMP levels within 1 minute following stimulation of rabbit neutrophils with chemotactic peptides or HSA.

Anaphylatoxins↗
PubMed1979

A membrane glycoprotein of aggregating Dictyostelium cells with the properties of contact sites.

Aggregating cells of Dictyostelium discoideum form EDTA-stable contacts which are blocked by a Fab (antigen-binding fragment) preparation from antisera raised against membranes. The target site of the blocking Fab fragments has been identified as a specific glycoprotein. In this paper its purification, carbohydrate and amino acid composition are described. Purification was 800-fold, starting with cells lysed by digitonin. The plasma membranes, preserved as ghosts by this treatment, were purified in a two-phase system and extracted with butan-1-ol. The water phase contained predominantly concanavalin-A-binding glycoproteins and was particularly rich in contact sites A. These were further purified on DE-cellulose and sucrose gradients. Sodium dodecylsulphate/polyacrylamide gel electrophoresis of the purified material revealed one major glycoprotein band in the molecular weight region of 80 000 to 90 000, depending on the acrylamide concentration. The sugars found in contact sites A were mannose, N-acetylglucosamine, fucose, and possibly glucose. The protein moeity contained 8% proline and was particularly rich in hydroxy amino acids.

Amino Acids↗
PubMed1979

Action of a slowly hydrolysable cyclic AMP analogue on developing cells of Dictyostelium discoideum.

Adenosine 3',5'-cyclic phosphorothioate (cAMP-S) is a cyclic AMP (cAMP) analogue which is only slowly hydrolysed by phosphodiesterases of Dictyostelium discoideum. The affinity of cAMP-S to cAMP receptors at the cell surface is only one order of magnitude lower than that of cAMP. cAMP-S can replace cAMP as a stimulant with respect to all receptor-mediated responses tested, including chemotaxis and the induction of cAMP pulses. cAMP-S does not affect growth of D. discoideum but it blocks cell aggregation at a uniform concentration of 5 x 10(-7) M in agar plate cultures of strain NC-4 as well as its axenically growing derivative, Ax-2. Another wild-type strain of D. discoideum, v-12, is able to aggregate on agar plates supplemented with 1 mM cAMP-S. The development of Polysphondylium pallidum and P. violaceum is also highly cAMP-S resistant. In Ax-2 both differentiation from the growth phase to the aggregation-competent stage and chemotaxis are cAMP-S sensitive, whereas in v-12 only chemotaxis is inhibited. v-12 can still form streams of cohering cells and fruiting bodies when chemotaxis is inhibited by cAMP-S. Whereas cAMP induces differentiation into stalk cells at concentrations of 10(-3) or 10(-4) M, cAMP-S has the same effect in strain v-12 at the much lower concentration of 10(-6) M.

Chemotaxis↗
PubMed1979

Oscillations of cyclic nucleotide concentrations in relation to the excitability of Dictyostelium cells.

Aggregating cells of Dictyostelium discoideum are able to release cyclic AMP periodically. The oscillations of cAMP generation are associated with changes in adenylate cyclase activity. Cyclic AMP receptors on the cell surface are functionally coupled to the oscillating system as evidenced by phase shifts that are induced by small pulses of extracellular cAMP. An important element of the oscillating system is the signal processing from surface receptors to the adenylate cyclase. This pathway exhibits adaptation resulting in the suppression of responses to constant, elevated concentrations of cAMP. The signal input for adenylate cyclase activation is, therefore, a change in the extracellular cAMP concentration with time. Oscillations in the absence of detectable changes of intra- or extracellular cAMP concentrations suggest the possibility that there is a metabolic network in D. discoideum cells that undergoes oscillations without coupling to adenylate cyclase. Cyclic GMP concentrations oscillate with a slight phase difference in advance of that of cAMP, suggesting that the two nucleotide cyclases might not be activated by the same mechanism. Elevation of extracellular calcium exerts an inhibitory effect on the accumulation of cAMP and on the second of the two cGMP peaks.

Adenylyl Cyclases↗
PubMed1978

A specific glycoprotein as the target site of adhesion blocking Fab in aggregating Dictyostelium cells.

During the acquisition of aggregation competence a new antigen appears on the surface of Dictyostelium cells. Univalent antibody fragments (Fab) against this antigen render the cells unable to form the specific type of cell adhesion which is characteristic of aggregating cells. This membrane constituent has been purified and identified as a concanavalin A-binding glycoprotein present at about 2 X 10(5) copies per cell.

Antibody Specificity↗
PubMed1978

Specific binding proteins for cyclic AMP and cyclic GMP in Dictyostelium discoideum.

In Dictyostelium discoideum both cyclic AMP and cyclic GMP are regulated by chemotactic stimuli. Binding proteins specific for cAMP and cGMP have been found in aggregation competent cells as well as in cells harvested during growth. The activity of binding proteins was, on the average, lower in the growth phase cells. cAMP binding proteins were separated into 3 fractions, whereas the cGMP binding activity appeared in 1 major peak both on DEAE-cellulose and Sephadex G-200. Protein kinase activity was present in most but not all cyclic necleotide binding fractions; evidence for a relationship is however missing.

Cell Cycle↗
PubMed1978

Cyclic GMP regulation and responses of Polysphondylium violaceum to chemoattractants.

In cells of the cellular slime mold Polysphondylium violaceum an attractant, which is released during the aggregation stage, causes a transient rise of the cyclic GMP concentration. Cells of this organism develop in shaken suspensions after they have finished growth. Cell development is not accompanied by an increase in the EDTA stability of cell adhesion. Both the developmental regulation and the specificity of chemotactic responses is reflected in the light scattering patterns recorded in cell suspensions: Folic acid causes a strong response in early preaggregation cells and the Polysphondylium attractant does the same in aggregation competent cells, whereas cyclic AMP is inactive in both stages.

Cell Aggregation↗
PubMed1978

Cyclic-AMP stimulated calcium influx into aggregating cells of Dictyostelium discoideum.

Within about 10 seconds after stimulation of Dictyostelium discoideum cells with cyclic AMP an increased rate of 45Ca influx was observed. Part of the cellular calcium reappeared in the extra-cellular medium between 1 and 3 minutes after stimulation. No effect of 5'AMP on calcium distribution was found. The transient calcium influx is discussed in connection with chemotaxis and other cyclic-AMP induced responses.

Calcium↗