Abstract
Phosphoinositides, the seven phosphorylated derivatives of phosphatidylinositol have emerged as regulators of key sub-cellular processes such as membrane transport, cytoskeletal function and plasma membrane signaling in eukaryotic cells. All of these processes are also present in the cells that constitute the nervous system of animals and in this setting too, these are likely to tune key aspects of cell biology in relation to the unique structure and function of neurons. Phosphoinositides metabolism and function are mediated by enzymes and proteins that are conserved in evolution, and analysis of knockouts of these in animal models implicate this signaling system in neural function. Most recently, with the advent of human genome analysis, mutations in genes encoding components of the phosphoinositide signaling pathway have been implicated in human diseases although the cell biological basis of disease phenotypes in many cases remains unclear. In this review we evaluate existing evidence for the involvement of phosphoinositide signaling in human nervous system diseases and discuss ways of enhancing our understanding of the role of this pathway in the human nervous system’s function in health and disease.
Highlights
Phosphoinositides, the seven phosphorylated derivatives of phosphatidylinositol have emerged as regulators of key sub-cellular processes such as membrane transport, cytoskeletal function and plasma membrane signaling in eukaryotic cells
Phosphoinositides are present in every cell type in eukaryota, given the long-established observation that inositol lipids are enriched in the brain, these lipids are likely to support key cellular functions in the human brain and alterations in these could lead to diseases of the nervous system
The addition of phosphates is performed by an evolutionarily conserved group of enzymes called the phosphoinositide kinases. These enzymes are selective in two respects (i) They are specific for the substrate molecule on which they will act: for example a lipid kinase may act only on phosphatidylinositol 5 phosphate (PI5P) but not phosphatidylinositol 4 phosphate (PI4P) (ii) They are specific for the OH group on the myo-inositol ring at which they will add the phosphate group: for example an enzyme that will only add a phosphate at position 4 but not position 5
Summary
Phosphoinositides, the seven phosphorylated derivatives of phosphatidylinositol have emerged as regulators of key sub-cellular processes such as membrane transport, cytoskeletal function and plasma membrane signaling in eukaryotic cells. Phosphoinositides are present in every cell type in eukaryota, given the long-established observation that inositol lipids are enriched in the brain, these lipids are likely to support key cellular functions in the human brain and alterations in these could lead to diseases of the nervous system.
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