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Phosphatidylinositol 4-kinases and PI4P metabolism in the nervous system: roles in psychiatric and neurological diseases.

Abstract
The four mammalian phosphatidylinositol 4-kinases, together with the PI(4,5)P(2) depleting 5-phosphatases of the oculocerebrorenal syndrome of Lowe and synaptojanin families, modulate neuronal pools of PI4P lipid and regulate intracellular membrane trafficking in the endocytic and secretory pathways. Dysfunctions in these enzymes have been associated with a broad spectrum of disorders including schizophrenia, bipolar disorder, Lowe syndrome, age-related neurodegeneration, Alzheimer's disease and Down syndrome. Recent work has shown that reduced expression of individual phosphatidylinositol 4-kinase isozymes is associated with impaired survival of specific neuronal populations within the CNS. Furthermore, alterations to the concentrations of different phosphoinositide lipid species in the brain and, in particular, the ratio of PI4P to PI(4,5)P(2) can have deleterious effects on clathrin-dependent membrane trafficking both in the Golgi-endosomal pathway and at the plasma membrane. In this article, we focus on the cell biology, biochemistry and neuronal functions of the phosphatidylinositol 4-kinases and their emerging roles in psychiatric and neurological pathologies.
AuthorsEmma L Clayton, Shane Minogue, Mark G Waugh
JournalMolecular neurobiology (Mol Neurobiol) Vol. 47 Issue 1 Pg. 361-72 (Feb 2013) ISSN: 1559-1182 [Electronic] United States
PMID23054682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 4-phosphate
  • 1-Phosphatidylinositol 4-Kinase
Topics
  • 1-Phosphatidylinositol 4-Kinase (metabolism)
  • Animals
  • Humans
  • Mental Disorders (enzymology, pathology)
  • Nervous System (enzymology, pathology)
  • Nervous System Diseases (enzymology, pathology)
  • Phosphatidylinositol Phosphates (metabolism)

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