Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 72-85 |
| Number of pages | 14 |
| Journal | NeuroSignals |
| Volume | 20 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2012 |
| Externally published | Yes |
ASJC Scopus Subject Areas
- Neurology
- Developmental Neuroscience
- Cellular and Molecular Neuroscience
Keywords
- Exocytosis
- GluR5
- Group IIA secretory phospholipase A
- Kainate receptors
- Neurotransmission
- Nociception
- Pain
- Protein kinase C
- Secretory phospholipase A
- Synaptic plasticity