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Start Over Author "Bandle RW" Topic sphingosine
2 results on '"Bandle RW"'

1. Sphingosine-1-phosphate initiates rapid retraction of pseudopodia by localized RhoA activation.

Author

Koh E, Clair T, Hermansen R, Bandle RW, Schiffmann E, Roberts DD, and Stracke ML

Subjects
Actins metabolism, Animals, Carrier Proteins antagonists & inhibitors, Carrier Proteins metabolism, Cell Adhesion drug effects, Cell Line, Cell Movement drug effects, Cell Polarity drug effects, Enzyme Activation drug effects, Formins, Humans, Intracellular Signaling Peptides and Proteins antagonists & inhibitors, Intracellular Signaling Peptides and Proteins metabolism, Mice, Microtubules drug effects, Microtubules metabolism, NIH 3T3 Cells, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases metabolism, Protein Transport drug effects, Sphingosine pharmacology, Vinculin metabolism, rac GTP-Binding Proteins metabolism, rho-Associated Kinases, rhoA GTP-Binding Protein antagonists & inhibitors, Lysophospholipids pharmacology, Pseudopodia drug effects, Pseudopodia enzymology, Sphingosine analogs & derivatives, rhoA GTP-Binding Protein metabolism
Abstract

Lysophosphatidic acid (LPA) stimulates sphingosine-1-phosphate (S1P)-sensitive motility in NIH3T3 clone7 cells. S1P inhibits motility only when added to the bottom well of the Boyden chamber, suggesting that pseudopodia can respond to their microenvironment. In order to study and localize this effect, we utilized a Transwell insert system to isolate pseudopodia. LPA stimulates protrusion of pseudopodia that are enriched in RhoA compared to cell bodies. Removal of LPA results in slow retraction with loss of vinculin-rich adhesion complexes and prolonged activation of RhoA. However, RhoA, ROCK and mDia are not required for this process. In contrast, rapid retraction, induced by adding S1P to the bottom well, is associated with a quick spike of activated RhoA and coalescence of adhesion complexes that colocalize with the ends of stress fibers. S1P-induced retraction requires RhoA and ROCK but is only delayed by inhibition of mDia. These data indicate that pseudopodia sense and integrate signals initiated by localized bioactive lipids, affecting both cellular polarity and their own function in motility.

Published
2007
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2. Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate.

Author

Clair T, Aoki J, Koh E, Bandle RW, Nam SW, Ptaszynska MM, Mills GB, Schiffmann E, Liotta LA, and Stracke ML

Subjects
3T3 Cells, Animals, COS Cells, Catalysis, Cell Movement physiology, Chlorocebus aethiops, Hydrolysis drug effects, Mice, Phosphodiesterase I, Phosphoric Diester Hydrolases, Pyrophosphatases, Receptors, Cell Surface biosynthesis, Receptors, Lysophospholipid, rho GTP-Binding Proteins metabolism, Glucose-6-Phosphate Isomerase pharmacology, Glycoproteins pharmacology, Lysophospholipids, Multienzyme Complexes, Phosphorylcholine analogs & derivatives, Phosphorylcholine metabolism, Receptors, G-Protein-Coupled, Sphingosine analogs & derivatives, Sphingosine biosynthesis, Sphingosine metabolism
Abstract

Autotaxin (ATX) is an exoenzyme that potently induces tumor cell motility, and enhances experimental metastasis and angiogenesis. ATX was shown recently to be identical to serum lysophospholipase D activity, producing lysophosphatidic acid (LPA) from lyso-glycerophospholipids. LPA, itself a strong chemoattractant for tumor cells, may mediate the actions of ATX. We now extend the substrate specificity to sphingosylphosphorylcholine (SPC), which ATX hydrolyzes to sphingosine-1-phosphate (S1P). Under migration assay conditions, this novel reaction for the production of S1P has a substrate (SPC) K(m) = 0.23 +/- 0.07 mM. In our responder cell lines (NIH3T3 clone7 and A2058), S1P exerts maximal biological effects at concentrations of 10-100 nM and is mimicked in its biological effects by ATX plus SPC. These effects include inhibition of ATX- and LPA-stimulated motility, and elevation of activated Rho. In NIH3T3 clone7 cells stimulated with platelet-derived growth factor and treated with 10-25 nM S1P, motility is not inhibited and activation of Rho is unaffected, indicating that S1P possesses specificity in its effects. The exoenzyme ATX can potentially regulate diverse processes such as motility and angiogenesis via the S1P family of receptors. Because ATX hydrolyzes nucleotides, lyso-glycerophospholipids, and phosphosphingolipids into bioactive products, it possesses the ability, depending on the availability of substrates, to act as positive or negative regulator of receptor-mediated activity in the cellular microenvironment.

Published
2003

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