Annexin A6-induced inhibition of cytoplasmic phospholipase A2 is linked to caveolin-1 export from the Golgi.
The molecular mechanisms regulating the exit of caveolin from the Golgi complex are not fully understood. Cholesterol and sphingolipid availability affects Golgi vesiculation events and involves the activity of cytoplasmic phospholipase A(2) (cPLA(2)). We recently demonstrated that high expression levels of annexin A6 (AnxA6) perturb the intracellular distribution of cellular cholesterol, thereby inhibiting caveolin export from the Golgi complex. In the present study we show that in Chinese hamster ovary cells overexpressing AnxA6, sequestration of cholesterol in late endosomes, leading to reduced amounts of cholesterol in the Golgi, inhibits cPLA(2) activity and its association with the Golgi complex. This correlates with the blockage of caveolin export from the Golgi in cells treated with methyl arachidonyl fluorophosphonate, a Ca(2+)-dependent cPLA(2) inhibitor. AnxA6-mediated down-regulation of cPLA(2) activity was overcome upon the addition of exogenous cholesterol or transfection with small interfering RNA targeting AnxA6. These findings indicate that AnxA6 interferes with caveolin transport through the inhibition of cPLA(2).
Cubells
Laia
L
Departament de Biologia Cellular, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Vilà de Muga
Sandra
S
Tebar
Francesc
F
Bonventre
Joseph V
JV
Balsinde
Jesús
J
Pol
Albert
A
Grewal
Thomas
T
Enrich
Carlos
C
D000818:Animals; D017317:Annexin A6 / Q000235:genetics / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D016466:CHO Cells; D019556:COS Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D013107:Sphingolipids / Q000378:metabolism
D017317:Annexin A6; D001095:Arachidonic Acids; D051242:Caveolin 1; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D034741:RNA, Small Interfering; D013107:Sphingolipids; C104810:methyl arachidonylfluorophosphonate; D002784:Cholesterol; D054510:Phospholipases A2, Cytosolic