phosphoinositides

Phosphoinositides (PIs) play an essential role in diverse cellular functions. Their intracellular level is strictly regulated by specific phosphoinositides kinases, phosphoinositides phosphatases and phosphoinositides phospholipases.

Phosphatidylinositol (PtdIns) and its phosphorylated derivatives represent less than 5% of total membrane phospholipids in cells. Despite their low abundance, they form a dynamic signalling system that is regulated in response to a variety of extra and intra-cellular cues.

Phosphoinositides and the enzymes that synthesize them are found in many different sub-cellular compartments including the nuclear matrix, heterochromatin, and sites of active RNA splicing, suggesting that phosphoinositides may regulate specific functions within the nuclear compartment.

The existence of distinct sub-cellular pools has led to the challenging task of understanding how the different pools are regulated and how changes in the mass of lipids within the nucleus can modulate nuclear specific pathways.

Phosphorylated forms of phosphatidylinositol are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking.

The inositol ring can be phosphorylated by a variety of kinases on the three, four and five hydroxyl groups in seven different combinations.

However, the two and six hydroxyl group is typically not phosphorylated due to steric hindrance.

Members

All seven variations of the following phosphoinositides have been found in animals:

 phosphatidylinositol monophosphates

• phosphatidylinositol 3-phosphate, also known as PtdIns3P or PI(3)P or 3-phosphoinositide
  — * phosphatidylinositol 4-phosphate, also known as PtdIns4P or PI(4)P
• phosphatidylinositol 5-phosphate, also known as PtdIns5P or PI(5)P

 phosphatidylinositol bisphophosphates

• phosphatidylinositol 3,4-bisphosphate, also known as PtdIns(3,4)P or PI(3,4)P2
• phosphatidylinositol 3,5-bisphosphate, also known as PtdIns(3,5)P or PI(3,5)P2
• phosphatidylinositol 4,5-bisphosphate, also known as PtdIns(4,5)P or PI(4,5)P2

 phosphatidylinositol trisphophosphate

• phosphatidylinositol 3,4,5-trisphosphate, also known as PtdIns(3,4,5)P or PI(3,4,5)P3

These phosphoinositides are also found in plant cells, with the exception of PIP3.

Pathology

 phosphoinositide signaling diseases

• PTEN-associated diseases
• Src homology 2-containing inositol-5-phosphatase phosphatases in acute myeloid leukemia or diabetes
• myotubularin family members in genetic diseases
• OCRL1 in Lowe syndrome

Features

 phosphoinositides signaling pathways

References

 Methods to assess changes in the pattern of nuclear phosphoinositides. Divecha N. Methods Mol Biol. 2010;645:165-77. PMID: 20645188

 Downes CP, Gray A, Lucocq JM. Probing phosphoinositide functions in signaling and membrane trafficking. Trends Cell Biol. 2005 May;15(5):259-68. PMID: 15866030

 Jones DR, Divecha N. Linking lipids to chromatin. Curr Opin Genet Dev. 2004 Apr;14(2):196-202. PMID: 15196467

 Pendaries C, Tronchere H, Plantavid M, Payrastre B. Phosphoinositide signaling disorders in human diseases. FEBS Lett. 2003 Jul 3;546(1):25-31. PMID: 12829232