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1

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A cell's sense of direction (1999)

C. A. Parent ; P. N. Devreotes

American Association for the Advancement of Science (AAAS)

In: Science. 284(5415): 765-70.

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Publication Date: 1999-04-30

Description: In eukaryotic cells directional sensing is mediated by heterotrimeric guanine nucleotide-binding protein (G protein)-linked signaling pathways. In Dictyostelium discoideum amoebae and mammalian leukocytes, the receptors and G-protein subunits are uniformly distributed around the cell perimeter. Chemoattractants induce the transient appearance of binding sites for several pleckstrin homology domain-containing proteins on the inner face of the membrane. In gradients of attractant these sites are persistently present on the side of the cell facing the higher concentration, even in the absence of a functional actin cytoskeleton or cell movement. Thus, the cell senses direction by spatially regulating the activity of the signal transduction pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parent, C A -- Devreotes, P N -- GM28007/GM/NIGMS NIH HHS/ -- GM47874/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):765-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10221901" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Cell Membrane/metabolism ; Chemotactic Factors/*physiology ; *Chemotaxis ; Chemotaxis, Leukocyte ; Dictyostelium/physiology ; GTP-Binding Proteins/*physiology ; Humans ; Leukocytes/physiology ; Receptors, Cell Surface/*physiology ; *Signal Transduction

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Localization of the G protein betagamma complex in living cells during chemotaxis (2000)

T. Jin ; N. Zhang ; Y. Long ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 287(5455): 1034-6.

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Publication Date: 2000-02-11

Description: Gradients of chemoattractants elicit signaling events at the leading edge of a cell even though chemoattractant receptors are uniformly distributed on the cell surface. In highly polarized Dictyostelium discoideum amoebas, membrane-associated betagamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) were localized in a shallow anterior-posterior gradient. A uniformly applied chemoattractant generated binding sites for pleckstrin homology (PH) domains on the inner surface of the membrane in a pattern similar to that of the Gbetagamma subunits. Loss of cell polarity resulted in uniform distribution of both the Gbetagamma subunits and the sensitivity of PH domain recruitment. These observations indicate that Gbetagamma subunits are not sufficiently localized to restrict signaling events to the leading edge but that their distribution may determine the relative chemotactic sensitivity of polarized cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jin, T -- Zhang, N -- Long, Y -- Parent, C A -- Devreotes, P N -- GM-28007/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1034-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669414" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Binding Sites ; Cell Membrane/metabolism ; Cell Polarity ; Chemotactic Factors/pharmacology ; Chemotaxis/*physiology ; Cyclic AMP/pharmacology ; Dictyostelium/metabolism/*physiology ; *GTP-Binding Protein beta Subunits ; *GTP-Binding Protein gamma Subunits ; GTP-Binding Proteins/*metabolism ; *Heterotrimeric GTP-Binding Proteins ; Recombinant Fusion Proteins/metabolism ; Signal Transduction

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

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In vivo receptor-mediated phosphorylation of a G protein in Dictyostelium (1990)

R. E. Gundersen ; P. N. Devreotes

American Association for the Advancement of Science (AAAS)

In: Science. 248(4955): 591-3.

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Publication Date: 1990-05-04

Description: Extracellular adenosine 3',5'-monophosphate (cAMP) serves multiple roles in Dictyostelium development, acting as a chemoattractant, a cell-cell signaling molecule, and an inducer of differentiation. The Dictyostelium G-protein alpha subunit G alpha 2 appears to be the major transducer linking the surface cAMP receptor to these intracellular responses. On stimulation of cells with cAMP, G alpha 2 is phosphorylated on one or more serine residues, resulting in an alteration of its electrophoretic mobility. Phosphorylation of G alpha 2 is triggered by increased occupancy of the surface cAMP receptor and is rapid and transient, coinciding with the time course of activation of physiological responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gundersen, R E -- Devreotes, P N -- 28007/PHS HHS/ -- New York, N.Y. -- Science. 1990 May 4;248(4955):591-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2110382" target="_blank"〉PubMed〈/a〉

Keywords: Cell Membrane/metabolism ; Dictyostelium/*metabolism ; GTP-Binding Proteins/isolation & purification/*metabolism ; Macromolecular Substances ; Phosphates/metabolism ; Phosphorus Radioisotopes ; Phosphorylation ; Phosphoserine/analysis ; Receptors, Cyclic AMP/*metabolism

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Electronic ISSN: 1095-9203

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Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer (2014)

H. Cai ; M. Katoh-Kurasawa ; T. Muramoto ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 343(6177): 1249531. doi: 10.1126/science.1249531.

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Publication Date: 2014-03-22

Description: Biological oscillations are observed at many levels of cellular organization. In the social amoeba Dictyostelium discoideum, starvation-triggered multicellular development is organized by periodic cyclic adenosine 3',5'-monophosphate (cAMP) waves, which provide both chemoattractant gradients and developmental signals. We report that GtaC, a GATA transcription factor, exhibits rapid nucleocytoplasmic shuttling in response to cAMP waves. This behavior requires coordinated action of a nuclear localization signal and reversible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor-mediated phosphorylation. Although both are required for developmental gene expression, receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle. We demonstrate that this biological circuit filters out high-frequency signals and counts those admitted, thereby enabling cells to modulate gene expression according to the dynamic pattern of the external stimuli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061987/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061987/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cai, Huaqing -- Katoh-Kurasawa, Mariko -- Muramoto, Tetsuya -- Santhanam, Balaji -- Long, Yu -- Li, Lei -- Ueda, Masahiro -- Iglesias, Pablo A -- Shaulsky, Gad -- Devreotes, Peter N -- GM 28007/GM/NIGMS NIH HHS/ -- GM 34933/GM/NIGMS NIH HHS/ -- HD 039691/HD/NICHD NIH HHS/ -- P01 HD039691/HD/NICHD NIH HHS/ -- R01 GM028007/GM/NIGMS NIH HHS/ -- R01 GM034933/GM/NIGMS NIH HHS/ -- R37 GM028007/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1249531. doi: 10.1126/science.1249531.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653039" target="_blank"〉PubMed〈/a〉

Keywords: Active Transport, Cell Nucleus ; Cell Nucleus/*metabolism ; Cyclic AMP/metabolism/pharmacology ; Cytoplasm/*metabolism ; Dictyostelium/growth & development/*metabolism ; GATA Transcription Factors/chemistry/genetics/*metabolism ; Gene Expression Regulation ; Heterotrimeric GTP-Binding Proteins/metabolism ; Nuclear Localization Signals ; Phosphorylation ; Protozoan Proteins/chemistry/genetics/*metabolism ; Receptors, G-Protein-Coupled/metabolism

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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5

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Adenosine 3',5'-monophosphate waves in Dictyostelium discoideum: a demonstration by isotope dilution--fluorography (1981)

K. J. Tomchik ; P. N. Devreotes

American Association for the Advancement of Science (AAAS)

In: Science. 212(4493): 443-6.

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Publication Date: 1981-04-24

Description: The distribution of adenosine 3',5'-monophosphate (cyclic AMP) in fields of aggregating amoebae of Dictyostelium discoideum was examined by a novel isotope dilution-fluorographic technique. Cellular cyclic AMP was visualized by its competition with exogenous 3H-labeled cyclic AMP for high-affinity binding sites on protein kinase immobilized on a Millipore filter used to blot the monolayer. The cyclic AMP was distributed in spiral or concentric circular wave patterns which centered on the foci of the aggregations. These patterns were correlated with those of cell shape change that propagate through the monolayers: cells in regions of high concentrations of cyclic AMP were elongated (presumably moving up a cyclic AMP gradient), whereas those in regions of low cyclic AMP concentrations were randomly directed. The highest cyclic AMP concentrations were about 10(-6)M. The widths of the regions of elevated cyclic AMP were about 0.3 to 1 millimeter which, assuming a wave velocity of 300 micrometers per minute, suggests that a cell signals for about 1 to 3 minutes. These observations support the hypothesis that the aggregation process in Dictyostelium is mediated by the periodic relay of cyclic AMP signals and suggest a simple scheme for the dynamics of the aggregation process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomchik, K J -- Devreotes, P N -- GM 22321/GM/NIGMS NIH HHS/ -- GM 28007/GM/NIGMS NIH HHS/ -- RR-5378/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1981 Apr 24;212(4493):443-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6259734" target="_blank"〉PubMed〈/a〉

Keywords: *Cell Aggregation ; Cell Communication ; Cyclic AMP/*metabolism ; Dictyostelium/cytology/*metabolism ; Fluorometry ; Time Factors

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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A chemoattractant receptor controls development in Dictyostelium discoideum (1988)

P. S. Klein ; T. J. Sun ; C. L. Saxe, 3rd ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 241(4872): 1467-72.

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Publication Date: 1988-09-16

Description: During the early stages of its developmental program, Dictyostelium discoideum expresses cell surface cyclic adenosine monophosphate (cyclic AMP) receptors. It has been suggested that these receptors coordinate the aggregation of individual cells into a multicellular organism and regulate the expression of a large number of developmentally regulated genes. The complementary DNA (cDNA) for the cyclic AMP receptor has now been cloned from lambda gt-11 libraries by screening with specific antiserum. The 2-kilobase messenger RNA (mRNA) that encodes the receptor is undetectable in growing cells, rises to a maximum at 3 to 4 hours of development, and then declines. In vitro transcribed complementary RNA, when hybridized to cellular mRNA, specifically arrests in vitro translation of the receptor polypeptide. When the cDNA is expressed in Dictyostelium cells, the undifferentiated cells specifically bind cyclic AMP. Cell lines transformed with a vector that expresses complementary mRNA (antisense) do not express the cyclic AMP receptor protein. These cells fail to enter the aggregation stage of development during starvation, whereas control and wild-type cells aggregate and complete the developmental program within 24 hours. The phenotype of the antisense transformants suggests that the cyclic AMP receptor is essential for development. The deduced amino acid sequence of the receptor reveals a high percentage of hydrophobic residues grouped in seven domains, similar to the rhodopsins and other receptors believed to interact with G proteins. It shares amino acid sequence identity and is immunologically cross-reactive with bovine rhodopsin. A model is proposed in which the cyclic AMP receptor crosses the bilayer seven times with a serine-rich cytoplasmic carboxyl terminus, the proposed site of ligand-induced receptor phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, P S -- Sun, T J -- Saxe, C L 3rd -- Kimmel, A R -- Johnson, R L -- Devreotes, P N -- GM 34933/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1988 Sep 16;241(4872):1467-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3047871" target="_blank"〉PubMed〈/a〉

Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Dictyostelium/*growth & development/physiology ; Membrane Proteins/physiology ; Molecular Sequence Data ; Protein Conformation ; Receptors, Cyclic AMP/*physiology ; Solubility

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

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7

Electronic Resource

Molecualr Genetics of Signal Transduction in Dictyostelium (1996)

Parent, C A ; Devreotes, P N

Palo Alto, Calif. : Annual Reviews

Annual Review of Biochemistry 65 (1996), S. 411-440

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ISSN: 0066-4154

Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff

Topics: Chemistry and Pharmacology , Biology

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1146/annurev.bi.65.070196.002211

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8

Electronic Resource

Molecular basis of localized responses during chemotaxis in amoebae and leukocytes (1999)

van Es, S. ; Devreotes, P. N.

Springer

Cellular and molecular life sciences 55 (1999), S. 1341-1351

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ISSN: 1420-9071

Keywords: Key words. Chemotaxis; Dictyostelium; leukocytes; chemoattractant receptors; G-proteins; signal transduction.

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Abstract. Free-living amoebae as well as mammalian leukocytes sense chemoattractants with seven helix receptors linked to G-proteins. The cells respond by extending pseudopods and moving in the direction of the highest concentration. Recent studies using GFP-tagged proteins in Dictyostelium have shown that the directional response becomes sharply localized downstream of the receptors and G-proteins but upstream of the actin cytoskeleton. These studies together with the isolation novel genes by insertional mutagenesis in Dictyostelium are leading to a new understanding of chemotaxis in eucaryotic cells.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s000180050374

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