title: Receptor-mediated regulation of peroxisomal motility in CHO and endothelial cells.
abstract: The regulation of peroxisomal motility was investigated both in CHO cells and in cells derived from human umbilical vein endothelium (HUE). The cells were transfected with a construct encoding the green fluorescent protein bearing the C-terminal peroxisomal targeting signal 1. Kinetic analysis following time-lapse imaging revealed that CHO cells respond to simultaneous stimulation with ATP and lysophosphatidic acid (LPA) by reducing peroxisomal movements. When Ca(2+) was omitted from the extracellular medium or the cells were incubated with inhibitors for heterotrimeric G(i)/G(o) proteins, phospholipase C, classical protein kinase C isoforms (cPKC), mitogen-activated protein kinase kinase (MEK) or phospholipase A(2) (PLA(2)), this signal-mediated motility block was abolished. HUE cells grown to confluency on microporous membranes responded similarly to ATP-LPA receptor co-stimulation, but only when the ligands had access to the basolateral membrane region. These data demonstrate that peroxisomal motility is subject to specific modulation from the extracellular environment and suggest a receptor-mediated signaling cascade comprising Ca(2+) influx, G(i)/G(o) proteins, phospholipase C, cPKC isoforms, MEK and PLA(2) being involved in the regulation of peroxisomal arrest.
authors.affiliation: Biochemie-Zentrum, Universität Heidelberg, D-69120 Heidelberg.
authors.forename: C M
authors.initials: CM
authors.lastname: Huber
authors.forename: R
authors.initials: R
authors.lastname: Saffrich
authors.forename: W
authors.initials: W
authors.lastname: Ansorge
authors.forename: W W
authors.initials: WW
authors.lastname: Just
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D016764:Cell Polarity; D002478:Cells, Cultured; D006224:Cricetinae; D003600:Cytosol / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D020675:Peroxisomes / Q000187:drug effects / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D010741:Phospholipases A