Intracellular Calcium Signals Regulating Cytosolic Phospholipase A2 Translocation to Internal Membranes* 210

Increased intracellular Ca2+concentrations ([Ca2+] i ) promote cytosolic phospholipase A2 (cPLA2) translocation to intracellular membranes. The specific membranes to which cPLA2 translocates and the [Ca2+] i signals required were investigated. Plasmids of EGFP fused to full-length cPLA2 (EGFP-FL) or to the cPLA2 C2 domain (EGFP-C2) were used in Ca2+/EGFP imaging experiments of cells treated with [Ca2+] i -mobilizing agonists. EGFP-FL and -C2 translocated to Golgi in response to sustained [Ca2+] i greater than ∼100–125 nm and to Golgi, ER, and perinuclear membranes (PNM) at [Ca2+] i greater than ∼210–280 nm. In response to short duration [Ca2+] i transients, EGFP-C2 translocated to Golgi, ER, and PNM, but EGFP-FL translocation was restricted to Golgi. However, EGFP-FL translocated to Golgi, ER, and PNM in response to long duration transients. In response to declining [Ca2+] i , EGFP-C2 readily dissociated from Golgi, but EGFP-FL dissociation was delayed. Agonist-induced arachidonic acid release was proportional to the [Ca2+] i and to the extent of cPLA2translocation. In summary, we find that the differential translocation of cPLA2 to Golgi or to ER and PNM is a function of [Ca2+] i amplitude and duration. These results suggest that the cPLA2 C2 domain regulates differential, Ca2+-dependent membrane targeting and that the catalytic domain regulates both the rate of translocation and enzyme residence.

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