Localization and function of cytosolic phospholipase A2alpha at the Golgi.
Cytosolic phospholipase A(2)alpha (cPLA(2)alpha, Group IVA phospholipase A(2)) is a central mediator of arachidonate release from cellular phospholipids for the biosynthesis of eicosanoids. cPLA(2)alpha translocates to intracellular membranes including the Golgi in response to a rise in intracellular calcium level. The enzyme's calcium-dependent phospholipid-binding C2 domain provides the targeting specificity for cPLA(2)alpha translocation to the Golgi. However, other features of cPLA(2)alpha regulation are incompletely understood such as the role of phosphorylation of serine residues in the catalytic domain and the function of basic residues in the cPLA(2)alpha C2 and catalytic domains that are proposed to interact with anionic phospholipids in the membrane to which cPLA(2)alpha is targeted. Increasing evidence strongly suggests that cPLA(2)alpha plays a role in regulating Golgi structure, tubule formation and intra-Golgi transport. For example, recent data suggests that cPLA(2)alpha regulates the transport of tight junction and adherens junction proteins through the Golgi to cell-cell contacts in confluent endothelial cells. However, there are now examples where data based on knockdown using siRNA or pharmacological inhibition of enzymatic activity of cPLA(2)alpha affects fundamental cellular processes yet these phenotypes are not observed in cells from cPLA(2)alpha deficient mice. These results suggest that in some cases there may be compensation for the lack of cPLA(2)alpha. Thus, there is continued need for studies employing highly specific cPLA(2)alpha antagonists in addition to genetic deletion of cPLA(2)alpha in mice.
Leslie
Christina C
CC
Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA. lesliec@njhealth.org
Gangelhoff
Todd A
TA
Gelb
Michael H
MH
D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology* / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D051379:Mice
D004791:Enzyme Inhibitors; D054513:Group IV Phospholipases A2