Group IVA phospholipase A2 is necessary for the biogenesis of lipid droplets
Gubern Burset, Albert (Universitat Autònoma de Barcelona. Institut de Neurociències)
Casas, Javier (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Biología y Genética Molecular)
Barceló Torns, Miquel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Barneda, David (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rosa, Xavier de la (Universitat Autònoma de Barcelona. Institut de Neurociències)
Masgrau Juanola, Roser (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Picatoste Ramón, Fernando (Universitat Autònoma de Barcelona. Institut de Neurociències)
Balsinde, Jesús (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Biología y Genética Molecular)
Balboa María, A. (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Biología y Genética Molecular)
Claro Izaguirre, Enrique (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2008
Resum:	Lipid droplets (LD) are organelles present in all cell types, consisting of a hydrophobic core of triacylglycerols and cholesteryl esters, surrounded by a monolayer of phospholipids and cholesterol. This work shows that LD biogenesis induced by serum, by long-chain fatty acids, or the combination of both in CHO-K1 cells was prevented by phospholipase A2 inhibitors with a pharmacological profile consistent with the implication of group IVA cytosolic phospholipase A2 (cPLA2α). Knocking down cPLA2α expression with short interfering RNA was similar to pharmacological inhibition in terms of enzyme activity and LD biogenesis. A Chinese hamster ovary cell clone stably expressing an enhanced green fluorescent protein-cPLA2α fusion protein (EGFP-cPLA2) displayed higher LD occurrence under basal conditions and upon LD induction. Induction of LD took place with concurrent phosphorylation of cPLA2α at Ser505. Transfection of a S505A mutant cPLA2α showed that phosphorylation at Ser505 is key for enzyme activity and LD formation. cPLA2α contribution to LD biogenesis was not because of the generation of arachidonic acid, nor was it related to neutral lipid synthesis. cPLA2α inhibition in cells induced to form LD resulted in the appearance of tubulo-vesicular profiles of the smooth endoplasmic reticulum, compatible with a role of cPLA2α in the formation of nascent LD from the endoplasmic reticulum.
Ajuts:	Ministerio de Educación y Ciencia SAF 2004-01698 Ministerio de Educación y Ciencia SAF 2007-60055
Nota:	Altres ajuts: MSPS/PI03/0528
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Arachidonic acids ; Basal conditions ; Cell types ; Chinese hamsters ; Cholesteryl esters ; Cytosolic phospholipase ; Endoplasmic reticulum ; Enhanced green fluorescent proteins ; Fusion proteins ; Hydrophobic cores ; In cells ; Lipid droplets ; Neutral lipids ; Pharmacological inhibitions ; Pharmacological profiles ; Phospholipase ; Short interfering ; Triacyl glycerols
Publicat a:	Journal of biological chemistry, Vol. 283, Num. 41 (2008) , p. 27369-27382, ISSN 1083-351X

DOI: 10.1074/jbc.M800696200
PMID: 18632668

14 p, 1.3 MB

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