Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An actin-related protein (ACLA) has been identified in the cellular slime mould Dictyostelium discoideum. The complete cDNA sequence indicates that within the actin superfamily it belongs to the ARP3 family of actin-related proteins together with Arp66B from Drosophila melanogaster, Actin2 from Bos taurus, act2 from Schizosaccharomyces pombe and possibly act2 from Caenorhabditis elegans. The ACLA mRNA is regulated during development, showing a maximum between 2 and 4 h after starvation. The protein has been expressed in E. coli and antibodies raised against it. Immunofluorescence microscopy shows that ACLA protein co-localises with mitochondria; the protein copurifies with Dictyostelium mitochondria.
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PMID:An actin-related protein from Dictyostelium discoideum is developmentally regulated and associated with mitochondria. 788 39

A few hours after the onset of starvation, amoebae of Dictyostelium discoideum start to form multicellular aggregates by chemotaxis to centers that emit periodic cyclic AMP signals. There are two major developmental decisions: first, the aggregates either construct fruiting bodies directly, in a process known as culmination, or they migrate for a period as "slugs." Second, the amoebae differentiate into either prestalk or prespore cells. These are at first randomly distributed within aggregates and then sort out from each other to form polarized structures with the prestalk cells at the apex, before eventually maturing into the stalk cells and spores of fruiting bodies. Developmental gene expression seems to be driven primarily by cyclic AMP signaling between cells, and this review summarizes what is known of the cyclic AMP-based signaling mechanism and of the signal transduction pathways leading from cell surface cyclic AMP receptors to gene expression. Current understanding of the factors controlling the two major developmental choices is emphasized. The weak base ammonia appears to play a key role in preventing culmination by inhibiting activation of cyclic AMP-dependent protein kinase, whereas the prestalk cell-inducing factor DIF-1 is central to the choice of cell differentiation pathway. The mode of action of DIF-1 and of ammonia in the developmental choices is discussed.
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PMID:Developmental decisions in Dictyostelium discoideum. 796 18

When freshly starved amoebae of Dictyostelium discoideum are stained with chlortetracycline (CTC), a cell type-specific fluorescent probe for membrane-associated calcium (CA2+) the resulting fluorescence distribution falls into two functional classes. Fluorescence-activated cell sorting shows that highly fluorescing amoebae tend to enter the prestalk pathway while those with low fluorescence tend to become prespores. In the light of previous findings, these results indicate that in addition to cell cycle phase at starvation, phenotypic variation in the level of sequestered calcium is an early correlate of cell fate.
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PMID:The level of sequestered calcium in vegetative amoebae of Dictyostelium discoideum can predict post-aggregative cell fate. 798 92

Cell differentiation in Dictyostelium results in the formation of two cell types, stalk and spore cells. The stalk cells undergo programmed cell death, whereas spore cells retain viability. The current evidence suggests that stalk cell differentiation is induced by Differentiation Inducing Factor (DIF), while spore cell differentiation occurs in response to cAMP. We have discovered the first developmentally regulated Dictyostelium gene, the glycogen phosphorylase gene 2 (gp2) gene, that can be induced by both DIF-1 and cAMP, suggesting the possibility of a new group of developmentally regulated genes that have DIF-1 and cAMP dual responsiveness. The gp2 gene was found to be expressed in both prestalk/stalk cells and prespore/spore cells. The DIF-1 competence of the gp2 gene required uninterrupted development, whereas the cAMP-competence for the gene required only starvation. Both DIF-1 and cAMP induction of the gene could be inhibited by NH3, a factor that is thought to act as a developmental signal in Dictyostelium. Another developmental signal, adenosine, was found to repress the DIF-1 induction of the gp2 gene. Two introns in the gp2 gene were examined for their involvement in the regulation of the gene, but no regulatory function was detected. A model for the regulation of the gp2 gene during the development is proposed.
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PMID:Dual regulation of the glycogen phosphorylase 2 gene Dictyostelium discoideum: the effects of DIF-1, cAMP, NH3 and adenosine. 802 27

The clathrin heavy chain is a major component of clathrin-coated vesicles that function in selective membrane traffic in eukaryotic cells. We disrupted the clathrin heavy chain gene (chcA) in Dictyostelium discoideum to generate a stable clathrin heavy chain-deficient cell line. Measurement of pinocytosis in the clathrin-minus mutant revealed a four-to five-fold deficiency in the internalization of fluid-phase markers. Once internalized, these markers recycled to the cell surface of mutant cells at wild-type rates. We also explored the involvement of clathrin heavy chain in the trafficking of lysosomal enzymes. Pulse chase analysis revealed that clathrin-minus cells processed most alpha-mannosidase to mature forms, however, approximately 20-25% of the precursor molecules remained uncleaved, were missorted, and were rapidly secreted by the constitutive secretory pathway. The remaining intracellular alpha-mannosidase was successfully targeted to mature lysosomes. Standard secretion assays showed that the rate of secretion of alpha-mannosidase was significantly less in clathrin-minus cells compared to control cells in growth medium. Interestingly, the secretion rates of another lysosomal enzyme, acid phosphatase, were similar in clathrin-minus and wild-type cells. Like wild-type cells, clathrin-minus mutants responded to starvation conditions with increased lysosomal enzyme secretion. Our study of the mutant cells provide in vivo evidence for roles for the clathrin heavy chain in (a) the internalization of fluid from the plasma membrane; (b) sorting of hydrolase precursors from the constitutive secretory pathway to the lysosomal pathway; and (c) secretion of mature hydrolases from lysosomes to the extracellular space.
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PMID:Clathrin heavy chain functions in sorting and secretion of lysosomal enzymes in Dictyostelium discoideum. 803 39

The sorting behavior of Dictyostelium discoideum Ax-2 cells and its relation to the cell-cycle phase at the onset of starvation were analyzed with reference to pattern formation, using beta-galactosidase as a cell marker and the temperature-shift method for cell synchronization. Cells transformed with the vector pAct15-Gal showed different sorting behavior during development when they were starved at different cell-cycle phases. Cells (T7) starved at the mid-late G2 phase (just before the PS-point from which cells enter the differentiation phase when starved) aggregated most rapidly and possibly functioned as aggregation centers, but were eventually sorted out to the posterior zone of migrating slugs. In contrast, T1 cells starved at the late G2 phase (just after the PS-point) exhibited slower aggregation compared with T7 cells. During further culture, T1 cells then sorted out to the apical tips of tipped aggregates and were located predominantly in the anterior zone of migrating slugs. Thus, T1 and T7 cells apparently interchange their positions in the cell masses during tip formation. The possible significance of cell-cycle-related sorting presented here is discussed, with special emphasis on pattern formation and cell differentiation.
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PMID:Cell-cycle-dependent sorting in the development of Dictyostelium cells. 812 89

The gene expressions associated with the switch-over from cell proliferation of Dictyostelium discoideum to differentiation have been analyzed using temperature shift and differential plaque hybridization methods. Quit1 was cloned as a specifically expressed gene when cells were starved just before the PS point (putative shift point from growth to differentiation). The coding region of the Quit1 gene is identical to that of the cAMP receptor 1 (CAR1) gene, which is essential for development. Quit1 mRNA was specifically expressed just after starvation of cells at around the PS point, thus indicating the importance of CAR1 for cellular differentiation as well as the actual existence of the PS point.
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PMID:Precise expression of the cAMP receptor gene, CAR1, during transition from growth to differentiation in Dictyostelium discoideum. 815 78

It has been suggested that cell-type determination in Dictyostelium discoideum is dependent on the position of a cell in the cell cycle at the time of starvation. In order to understand the molecular basis of this phenomenon, we initiated studies on the cell cycle and have recently described the isolation of a Dictyostelium gene encoding a homolog of the Cdc2 kinase. We have been unable to isolate additional cdc2 genes from Dictyostelium using polymerase chain reaction technology, but have isolated a gene that is highly related to cdc2. The encoded product is a protein of 33 kDa that shares over 60% identity to the cell-cycle-dependent Cdc2 kinases. However, despite this high level of identity, the gene is not capable of complementing the temperature-sensitive cdc28 mutant of Saccharomyces cerevisiae. Furthermore, the gene product shares some characteristics with the recently described PCTAIRE proteins; it contains a PCTAIRE motif instead of the Cdc2 kinase conserved PSTAIRE sequence, it does not possess the conserved GDSEID sequence that is involved in the activation of the enzyme and it has a Ser in the position equivalent to Thr-161. However, the Dictyostelium protein exhibits a slightly higher level of identity to the Cdc2 kinases than to the PCTAIRE proteins and is smaller than any of the PCTAIRE proteins thus far identified. Since the gene product has characteristics of both Cdc2 kinases and PCTAIRE proteins we have designated the gene product Crp (Cdc2-Related PCTAIRE) kinase. The gene is expressed as two transcripts of 1.5 and 1.8 kb and the expression is developmentally regulated with low levels of mRNA in vegetative cells and significantly higher levels throughout the remainder of the differentiation process. These results suggest the possibility that the gene product is involved in Dictyostelium differentiation rather than growth. This report is the first evidence for a highly-related cdc2 gene in unicellular eukaryote. It also demonstrates for the first time that a unicellular eukaryote expresses a protein containing the PCTAIRE sequence.
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PMID:The isolation from a unicellular organism, Dictyostelium discoideum, of a highly-related cdc2 gene with characteristics of the PCTAIRE subfamily. 821 53

The cellular slime mould Dictyostelium discoideum shows several responses after stimulation with the chemoattractant cAMP, including a transient rise in cyclic AMP (cAMP), cGMP and Ins(1,4,5)P3. In this paper the regulation of phospholipase C in vitro is described. Under our experimental conditions commercial PtdIns(4,5)P2 cannot be used to analyse phospholipase C activity in Dictyostelium lysates, because it is hydrolysed mainly to glycerophosphoinositol instead of Ins(1,4,5)P3. Enzyme activity was determined with endogenous unlabelled PtdInsP2 as a substrate. The product was measured by isotope-dilution assay and identified as authentic Ins(1,4,5)P3. Since phospholipase C is strictly Ca(2+)-dependent, with an optimal concentration range of 1-100 microM, cell lysates were prepared in EGTA and the enzyme reaction was started by adding 10 microM free Ca2+. Phospholipase C activity increased 2-fold during Dictyostelium development up to 8 h of starvation, after which the activity declined to less than 10% of the vegetative level. Enzyme activity in vitro increased up to 2-fold after stimulation of cells with the agonist cAMP in vivo. Addition of 10 microM guanosine 5'-[gamma-thio]triphosphate during lysis activated the enzyme to the same extent, and this effect was antagonized by guanosine 5'-[beta-thio]diphosphate. These results strongly suggest that surface cAMP receptors and G-proteins regulate phospholipase C during Dictyostelium development.
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PMID:Phospholipase C in Dictyostelium discoideum. Cyclic AMP surface receptor and G-protein-regulated activity in vitro. 828 97

The complete sequence of the Dictyostelium myosin ID (DMID) heavy chain isoform has been determined from cDNA and genomic clones. Like the DMIB isoform characterized previously, the DMID isoform is up-regulated during starvation-induced chemotactic aggregation, and its 124-kDa heavy chain contains the tail domain sequences that correspond to both the membrane and second actin-binding sites. An antibody that is specific for the DMID isoform was found to stain the actin-rich pseudopods at the leading edge of migrating cells. Protein microsequencing data reveals that the myosin I isoform localized to leading edge pseudopods in a previous study (Fukui, Y., Lynch, T. J., Brzeska, H., and Korn, E. D. (1989) Nature 341, 328-331) was DMIB, indicating that DMID and DMIB also colocalize and that both should influence the dynamics of actin-rich cortical structures. This and other data indicate that the DMID and DMIB isoforms are closely related and are distinct from the DMIA and DMIE isoforms, which possess truncated tail domains and are not up-regulated during chemotactic aggregation. Cells in which the DMID gene was rendered nonfunctional by targeted gene disruption do not show obvious behavioral defects, suggesting that another myosin I isoform(s) (possibly DMIB) might compensate for DMID. Finally, Southern blot data indicate that Dictyostelium may contain as many as nine myosin I isoforms.
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PMID:Sequence, expression pattern, intracellular localization, and targeted disruption of the Dictyostelium myosin ID heavy chain isoform. 832 74


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