Phosphatidylinositol in Transmembrane Signaling

As shown in Figure 14.6, a proportion of the phosphatidylinositol in membranes undergoes two successive phosphorylations to yield phosphatidylinos-itol bisphosphate. This is a substrate for hormone-sensitive phospholipase C, which is activated by the G-protein-GTP complex released into the cell membrane by a hormone receptor following binding of the hormone at the outer surface of the membrane. Phospholipase C hydrolyzes phosphatidylinositol bisphosphate to release diacylglycerol and inositol trisphosphate.

Inositol trisphosphate opens a calcium transport channel in the membrane of the endoplasmic reticulum. This leads to an influx of calcium from storage in the endoplasmic reticulum and a 10-fold increase in the cytosolic concentration of calcium ions. Calmodulin is a small calcium binding protein found in all cells. Its affinity for calcium is such that, at the resting concentration of calcium in the cytosol (of the order of 0.1 ^mol per L), little or none is bound to calmodulin. When the cytosolic concentration of calcium rises to about 1 ^mol per L, as occurs in response to opening of the endoplasmic reticulum calcium transport channel, calmodulin binds 4 mol of calcium per mol of protein. When this occurs, calmodulin undergoes a conformational change, and calcium-calmodulin binds to, and activates, cytosolic protein kinases, which in turn phosphorylate target enzymes.

The diacylglycerol released by phospholipase C action remains in the membrane, where it activates a membrane-bound protein kinase. It may also diffuse into cytosol, where it enhances the binding of calcium-calmodulin to cytosolic protein kinase.

Inositol trisphosphate is inactivated by further phosphorylation to inositol tetrakisphosphate, and diacylglycerol is inactivated by hydrolysis to glycerol and fatty acids.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook


Post a comment