Biomaterial Database

Cell density sensing mediated by a G protein-coupled receptor activating phospholipase C. 1998

D T Brazill, and D F Lindsey, and J D Bishop, and R H Gomer

Howard Hughes Medical Institute, Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, Texas 77005-1892, USA.

When the unicellular eukaryote Dictyostelium discoideum starves, it senses the local density of other starving cells by simultaneously secreting and sensing a glycoprotein called conditioned medium factor (CMF). When the density of starving cells is high, the corresponding high density of CMF permits signal transduction through cAR1, the chemoattractant cAMP receptor. cAR1 activates a heterotrimeric G protein whose alpha-subunit is Galpha2. CMF regulates cAMP signal transduction in part by regulating the lifetime of the cAMP-stimulated Galpha2-GTP configuration. We find here that guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) inhibits the binding of CMF to membranes, suggesting that the putative CMF receptor is coupled to a G protein. Cells lacking Galpha1 (Galpha1 null) do not exhibit GTPgammaS inhibition of CMF binding and do not exhibit CMF regulation of cAMP signal transduction, suggesting that the putative CMF receptor interacts with Galpha1. Work by others has suggested that Galpha1 inhibits phospholipase C (PLC), yet when cells lacking either Galpha1 or PLC were starved at high cell densities (and thus in the presence of CMF), they developed normally and had normal cAMP signal transduction. We find that CMF activates PLC. Galpha1 null cells starved in the absence or presence of CMF behave in a manner similar to control cells starved in the presence of CMF in that they extend pseudopods, have an activated PLC, have a low cAMP-stimulated GTPase, permit cAMP signal transduction, and aggregate. Cells lacking Gbeta have a low PLC activity that cannot be stimulated by CMF. Cells lacking PLC exhibit IP3 levels and cAMP-stimulated GTP hydrolysis rates intermediate to what is observed in wild-type cells starved in the absence or in the presence of an optimal amount of CMF. We hypothesize that CMF binds to its receptor, releasing Gbetagamma from Galpha1. This activates PLC, which causes the Galpha2 GTPase to be inhibited, prolonging the lifetime of the cAMP-activated Galpha2-GTP configuration. This, in turn, allows cAR1-mediated cAMP signal transduction to take place.

UI	MeSH Term	Description	Entries
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D002450	Cell Communication	Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.	Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002452	Cell Count	The number of CELLS of a specific kind, usually measured per unit volume or area of sample.	Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D004023	Dictyostelium	A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.	Dictyostelium discoideum,Dictyostelium discoideums,Dictyosteliums,discoideum, Dictyostelium
D005656	Fungal Proteins	Proteins found in any species of fungus.	Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001119	Arginase	A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ornithine (ORNITHINE) and urea. Deficiency of this enzyme causes HYPERARGININEMIA. EC 3.5.3.1.	Arginase A1,Arginase A4,Hepatic Proliferation Inhibitor,Liver Immunoregulatory Protein,Liver-Derived Inhibitory Protein,Liver-Derived Lymphocyte Proliferation Inhibiting Protein,Immunoregulatory Protein, Liver,Inhibitor, Hepatic Proliferation,Inhibitory Protein, Liver-Derived,Liver Derived Inhibitory Protein,Liver Derived Lymphocyte Proliferation Inhibiting Protein,Proliferation Inhibitor, Hepatic,Protein, Liver Immunoregulatory,Protein, Liver-Derived Inhibitory
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal