Cytosolic PLA₂ activation in Purkinje neurons and its role in AMPA-receptor trafficking

Cytosolic phospholipase A₂ (cPLA₂) selectively releases arachidonic acid from membrane phospholipids and has been proposed to be involved in the induction of long-term depression (LTD), a form of synaptic plasticity in the cerebellum. This enzyme requires two events for its full activation: Ca²⁺-dependent translocation from the cytosol to organelle membranes in order to access phospholipids as substrates, and phosphorylation by several kinases. However, the subcellular distribution and activation of cPLA₂ in Purkinje cells and the role of arachidonic acid in cerebellar LTD have not been fully elucidated. In cultured Purkinje cells, stimulation of AMPA receptors, but not metabotropic glutamate receptors, triggered translocation of cPLA₂ to the somatic and dendritic Golgi compartments. This translocation required Ca²⁺ influx through P-type Ca²⁺ channels. AMPA plus PMA, a chemical method for inducing LTD, released arachidonic acid via phosphorylation of cPLA₂. AMPA plus PMA induced a decrease in surface GluR2 for more than 2 hours. Interestingly, this reduction was occluded by a cPLA₂-specific inhibitor. Furthermore, PMA plus arachidonic acid caused the prolonged internalization of GluR2 without activating AMPA receptors. These results suggest that cPLA₂ regulates the persistent decrease in the expression of AMPA receptors, underscoring the role of cPLA₂ in cerebellar LTD.