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PLD1 and ERK2 regulate cytosolic lipid droplet formation
Linda Andersson1,*,
Pontus Boström1,*,
Johanna Ericson1,
Mikael Rutberg1,
Björn Magnusson1,
Denis Marchesan1,
Michel Ruiz1,
Lennart Asp1,
Ping Huang2,
Michael A. Frohman2,
Jan Borén1, and
Sven-Olof Olofsson1,
1 Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden 2 Department of Pharmacological Science and the Center for Developmental Genetics, Stony Brook University, Stony Brook, New York 11794, USA
Author for correspondence (e-mail: Sven-Olof.Olofsson{at}wlab.gu.se)
Accepted for publication 15 February 2006.
Abstract:
We have previously uncovered roles for phospholipase D (PLD)and an unknown cytosolic protein in the formation of cytosoliclipid droplets using a cell-free system. In this report, PLD1has been identified as the relevant isoform, and extracellularsignal-regulated kinase 2 (ERK2) as the cytosolic protein. Increasedexpression of PLD1 increased lipid droplet formation whereasknockdown of PLD1 using siRNA was inhibitory. A role for ERK2in basal lipid droplet formation was revealed by overexpressionor microinjection, and ablation by siRNA knockdown or pharmacologicalinhibition. Similar manipulations of other Map kinases suchas ERK1, JNK1 or JNK2 and p38 or p38ß were withouteffect. Insulin stimulated the formation of lipid droplets andthis stimulation was inhibited by knockdown of PLD1 (by siRNA)and by inhibition or knockdown (by siRNA) of ERK2. Inhibitionof ERK2 eliminated the effect of PLD1 on lipid droplet formationwithout affecting PLD1 activity, suggesting that PLD1 functionsupstream of ERK2. ERK2 increased the phosphorylation of dyneinwhich increased the amount of the protein on ADRP-containinglipid droplets. Microinjection of antibodies to dynein stronglyinhibited the formation of lipid droplets, demonstrating thatdynein has a central role in this formation. Thus dynein isa possible target for ERK2.
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or p38ß were without effect. Insulin stimulated the formation of lipid droplets and this stimulation was inhibited by knockdown of PLD1 (by siRNA) and by inhibition or knockdown (by siRNA) of ERK2. Inhibition of ERK2 eliminated the effect of PLD1 on lipid droplet formation without affecting PLD1 activity, suggesting that PLD1 functions upstream of ERK2. ERK2 increased the phosphorylation of dynein which increased the amount of the protein on ADRP-containing lipid droplets. Microinjection of antibodies to dynein strongly inhibited the formation of lipid droplets, demonstrating that dynein has a central role in this formation. Thus dynein is a possible target for ERK2. 
