title: Cytosolic phospholipase A(2) regulates golgi structure and modulates intracellular trafficking of membrane proteins.
abstract: The Golgi complex and the trans-Golgi network are critical cellular organelles involved in the endocytic and biosynthetic pathways of protein trafficking. Lipids have been implicated in the regulation of membrane-protein trafficking, vesicular fusion, and targeting. We have explored the role of cytosolic group IV phospholipase A(2) (cPLA(2)) in membrane-protein trafficking in kidney epithelial cells. Adenoviral expression of cPLA(2) in LLC-PK(1) kidney epithelial cells prevents constitutive trafficking to the plasma membrane of an aquaporin 2-green fluorescent protein chimera, with retention of the protein in the rough endoplasmic reticulum. Plasma membrane Na(+)-K(+)-ATPase alpha-subunit localization is markedly reduced in cells expressing cPLA(2), whereas the trafficking of a Cl(-)/HCO(3)(-) anion exchanger to the plasma membrane is not altered in these cells. Expression of cPLA(2) results in dispersion of giantin and beta-COP from their normal, condensed Golgi localization, and in marked disruption of the Golgi cisternae. cPLA(2) is present in Golgi fractions from noninfected LLC-PK(1) cells and rat kidney cortex. The distribution of tubulin and actin was not altered by cPLA(2), indicating that the microtubule and actin cytoskeleton remain intact. Total cellular protein synthesis is unaffected by the increase in cPLA(2) activity. Thus cPLA(2) plays an important role in determining Golgi architecture and selective control of constitutive membrane-protein trafficking in renal epithelial cells.
authors.affiliation: Renal Unit and Program in Membrane Biology, and. Cardiovascular Research Center, Medical Services, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129-2060, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Choukroun
authors.forename: V
authors.initials: V
authors.lastname: Marshansky
authors.forename: C E
authors.initials: CE
authors.lastname: Gustafson
authors.forename: M
authors.initials: M
authors.lastname: McKee
authors.forename: R J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: A
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D017920:Antiporters / Q000302:isolation & purification; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000302:isolation & purification; D002451:Cell Compartmentation; D016764:Cell Polarity; D048429:Cell Size; D027963:Chloride-Bicarbonate Antiporters; D003600:Cytosol / Q000201:enzymology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology; D006056:Golgi Apparatus / Q000648:ultrastructure*; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000302:isolation & purification
chemical_list: D017920:Antiporters; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D011994:Recombinant Proteins; D010741:Phospholipases A; D000254:Sodium-Potassium-Exchanging ATPase