Cytosolic PLA2(alpha) activation in Purkinje neurons and its role in AMPA-receptor trafficking.
Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) 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: Ca(2+)-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 cPLA(2)alpha 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 cPLA(2)alpha to the somatic and dendritic Golgi compartments. This translocation required Ca(2+) influx through P-type Ca(2+) channels. AMPA plus PMA, a chemical method for inducing LTD, released arachidonic acid via phosphorylation of cPLA(2)alpha. AMPA plus PMA induced a decrease in surface GluR2 for more than 2 hours. Interestingly, this reduction was occluded by a cPLA(2)alpha-specific inhibitor. Furthermore, PMA plus arachidonic acid caused the prolonged internalization of GluR2 without activating AMPA receptors. These results suggest that cPLA(2)alpha regulates the persistent decrease in the expression of AMPA receptors, underscoring the role of cPLA(2)alpha in cerebellar LTD.
Mashimo
Masato
M
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
Hirabayashi
Tetsuya
T
Murayama
Toshihiko
T
Shimizu
Takao
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D020865:Calcium Channels, P-Type; D018091:Receptors, AMPA; D016718:Arachidonic Acid; D018698:Glutamic Acid; D054513:Group IV Phospholipases A2; D002118:Calcium