Neuronal phospholipid deacylation is essential for axonal and synaptic integrity

作者：Glynn Paul^*

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2013, 1831(3): 633-641.

DOI：10.1016/j.bbalip.2012.07.023

• Neurological disease
• Axon degeneration
• Phospholipid turnover

Recessively-inherited deficiency in the catalytic activity of calcium-independent phospholipase A2-beta (iPLA2 beta) and neuropathy target esterase (NTE) causes infantile neuroaxonal dystrophy and hereditary spastic paraplegia, respectively. Thus, these two related phospholipases have non-redundant functions that are essential for structural integrity of synapses and axons. Both enzymes are expressed in essentially all neurons and also have independent roles in glia. iPLA2 beta liberates sn-2 fatty acid and lysophospholipids from diacylphospholipids. Ca2+-calmodulin tonically-inhibits iPLA2 beta, but this can be alleviated by oleoyl-CoA. Together with fatty acyl-CoA-mediated conversion of lysophospholipid to diacyl-phospholipid this may regulate sn-2 fatty acyl composition of phospholipids. In the nervous system, iPLA2 beta is especially important for the turnover of polyunsaturated fatty acid-associated phospholipid at synapses. More information is required on the interplay between iPLA2 beta and iPLA2-gamma in deacylation of neuronal mitochondrial phospholipids. NTE reduces levels of phosphatidylcholine (PtdCho) by degrading it to glycerophosphocholine and two free fatty acids. The substrate for NTE may be nascent PtdCho complexed with a phospholipid-binding protein. Protein kinase A-mediated phosphorylation enhances PtdCho synthesis and may allow PtdCho accumulation by coordinate inhibition of NTE activity. NTE operates primarily at the endoplasmic reticulum in neuronal soma but is also present in axons. NTE-mediated PtdCho homeostasis facilitates membrane trafficking and this appears most critical for the integrity of axon terminals in the spinal cord and hippocampus. For maintenance of peripheral nerve axons, iPLA2 beta activity may be able to compensate for NTE-deficiency but not vice-versa. Whether agonists acting at neuronal receptors modulate the activity of either enzyme remains to be determined. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.

• 出版日期2013-3