Mutants of Polysphondylium pallidum showing delayed modifications of glycoproteins are altered in a regulatory signal for development

1987 ◽  
Vol 87 (1) ◽  
pp. 121-132
Author(s):  
K. Toda ◽  
D. Francis ◽  
G. Gerisch
Keyword(s):  
Monoclonal Antibody ◽  
Early Stage ◽  
Developmental Regulation ◽  
Cell Aggregation ◽  
Carbohydrate Structure ◽  
Wild Type ◽  
Polysphondylium Pallidum ◽  
Carbohydrate Epitope ◽  
Regulatory Signal ◽  
Cell Surface Glycoproteins

Binding of a monoclonal antibody, mAb293, to cell-surface glycoproteins of Polysphondylium pallidum is known to be blocked by L-fucose, and Fab of this antibody has been shown to inhibit intercellular adhesion of aggregation-competent cells. Mutants with delayed expression of the carbohydrate epitope, ep293, recognized by the antibody, have been shown to be retarded and altered in cell aggregation. The present study shows that ep293 is a modification of carbohydrate structure that is subject to regulation not only in mutant but also in wild-type cells; ep293 is expressed at an early stage of exponential growth in wild-type and only after 12 h of starvation in mutant PN6002. Proteins are already glycosylated before the epitope is expressed. The developmental regulation of pallidin, a lectin known to be an unglycosylated protein, was investigated in parallel with ep293 using a monoclonal antibody. Pallidin was expressed at about the same time as the carbohydrate epitope in cells of the wild-type as well as the mutant. These results indicate a regulatory signal to which various events are coupled. Induction of ep293 and expression of pallidin are two of these events, and mutants such as PN6002 are altered in the timing of the signal.

scholarly journals Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma

2018 ◽  
Vol 25 (2) ◽  
pp. 145-162 ◽  
Author(s):  
Sara Molatore ◽  
Andrea Kügler ◽  
Martin Irmler ◽  
Tobias Wiedemann ◽  
Frauke Neff ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Early Stage ◽  
Pituitary Tumors ◽  
Transcriptome Profiling ◽  
Thyroid Neoplasms ◽  
Recessive Trait ◽  
Wild Type ◽  
Incurable Cancer ◽  
Medullary Thyroid ◽  
Adrenal Pheochromocytoma

Rats affected by the MENX syndrome spontaneously develop multiple neuroendocrine tumors (NETs) including adrenal, pituitary and thyroid gland neoplasms. MENX was initially reported to be inherited as a recessive trait and affected rats were found to be homozygous for the predisposingCdkn1bmutation encoding p27. We here report that heterozygous MENX-mutant rats (p27+/mut) develop the same spectrum of NETs seen in the homozygous (p27mut/mut) animals but with slower progression. Consequently, p27+/mut rats have a significantly shorter lifespan compared with their wild-type (p27+/+) littermates. In the tumors of p27+/mut rats, the wild-typeCdkn1ballele is neither lost nor silenced, implying that p27 is haploinsufficient for tumor suppression in this model. Transcriptome profiling of rat adrenal (pheochromocytoma) and pituitary tumors having different p27 dosages revealed a tissue-specific, dose-dependent effect of p27 on gene expression. In p27+/mut rats, thyroid neoplasms progress to invasive and metastatic medullary thyroid carcinomas (MTCs) accompanied by increased calcitonin levels, as in humans. Comparison of expression signatures of late-stage vs early-stage MTCs from p27+/mut rats identified genes potentially involved in tumor aggressiveness. The expression of a subset of these genes was evaluated in human MTCs and found to be associated with aggressive RET-M918T-positive tumors. Altogether, p27 haploinsufficiency in MENX rats uncovered a novel, representative model of invasive and metastatic MTC exploitable for translational studies of this often aggressive and incurable cancer.

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

scholarly journals Determination of Carbohydrate Structure Recognized by Prostate-specific F77 Monoclonal Antibody through Expression Analysis of Glycosyltransferase Genes

2014 ◽  
Vol 289 (23) ◽  
pp. 16478-16486 ◽  
Author(s):  
Motohiro Nonaka ◽  
Michiko N. Fukuda ◽  
Chao Gao ◽  
Zhen Li ◽  
Hongtao Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Expression Analysis ◽  
Carbohydrate Structure

scholarly journals Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

1998 ◽  
Vol 18 (10) ◽  
pp. 5744-5749 ◽  
Author(s):  
Irene Verkerke-Van Wijk ◽  
Ji-Yun Kim ◽  
Raymond Brandt ◽  
Peter N. Devreotes ◽  
Pauline Schaap
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Dictyostelium Discoideum ◽  
Developmental Regulation ◽  
Mutant Cell ◽  
Gene Induction ◽  
Specific Gene ◽  
Wild Type ◽  
Animal Development ◽  
Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 715-722 ◽  
Author(s):  
M. Torres ◽  
L. Sanchez
Keyword(s):  
In Situ Hybridization ◽  
Heat Shock ◽  
Dosage Compensation ◽  
Early Stage ◽  
Dual Function ◽  
Transcriptional Level ◽  
Wild Type ◽  
Blastoderm Stage ◽  
State Of Activity

The gene scute (sc) has a dual function: the scute function which is involved in neurogenesis and the sisterless-b function which is involved in generating the X:A signal that determines the state of activity of Sxl, a gene that controls sex determination and dosage compensation. We show here that the lethal phase of sc- females is embryonic and caused by the lack of Sxl function. We also analyze the time in development when sc and Sxl interact by means of (a) determining the thermosensitive phase (TSP) of the interaction between Sxl and sc and (b) a chimeric gene in which sc is under the control of a heat-shock promoter (HSSC-3). Pulses of sc expression from the HSSC-3 activate Sxl only at a very specific and early stage in development, which coincides with the TSP of the interaction between sc and Sxl. It corresponds to the syncytial blastoderm stage and coincides with the time when the X:A signal regulates Sxl. At this stage sc undergoes a homogeneous transient expression in wild-type flies. We conclude that the sc expression at the syncytial blastoderm is responsible for its sisterless-b function. Since sc expression from the HSSC-3 fully suppresses the sisterless-b phenotype, we further conclude that the sisterless-b function is exclusively provided by the sc protein. Finally, we have analyzed, by in situ hybridization, the effect of sc and sis-a mutations on the embryonic transcription of Sxl. Our results support the view that the control of Sxl by the X:A signal occurs at the transcriptional level.

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

1979 ◽  
Vol 35 (1) ◽  
pp. 321-338
Author(s):  
C. Rossier ◽  
G. Gerisch ◽  
D. Malchow
Keyword(s):  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Type Strain ◽  
Wild Type Strain ◽  
Agar Plate ◽  
Cell Aggregation ◽  
Fruiting Bodies ◽  
Wild Type ◽  
Camp Analogue ◽  
Order Of Magnitude

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 × 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.

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