Kainate receptors mediate regulated exocytosis of secretory phospholipase A(2) in SH-SY5Y neuroblastoma cells.
Secretory phospholipase A(2) (sPLA(2)) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA(2) (sPLA(2)-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA(2) is itself released, and a possible relation between glutamate receptors and sPLA(2) exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA(2)-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA(2)-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA(2)-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA(2)-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA(2)-IIA secretion. Moreover, KA-induced sPLA(2)-IIA secretion is dependent on Ca(2+) and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA(2) secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.
Division of Bioengineering, Nanyang Technological University, Singapore, Singapore.
Aung
A
Than
Yan
Y
Tan
Wei-Yi
WY
Ong
Akhlaq A
AA
Farooqui
Peng
P
Chen
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D054501:Group II Phospholipases A2 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D054501:Group II Phospholipases A2; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid