Phosphatidylinositol Signalling

Phosphatidylinositol Signalling
Page updated 20/1/03
All cells face a problem. They must all be capable of sensing chemical signals sent by other cells, or food sources but these are present at very low concentrations outside the cell and cannot pass through the outer cell membrane. What the cell (any cell) needs in a range of chemical sensors on the surface that are capable of detecting the presence of these signals, an amplifier to increase sensitivity, and a means to get the message across the membrane. It turns out that a component of the lipid bi-layer, phosphatidylinositol is pivotally involved in these processes.
	Figure 1. Biological membrane. Lipids have hydrophilic head-groups and hydrophobic tails. The tails stick together making a lipid sandwich. Trans-membranous proteins (red) are exposed both outside and inside the cell membrane. Whereas membranous proteins (blue) bind the membrane or are partially buried in it. The membrane is impervious to small molecules.
Cells have developed many ways to transducer signals from outside the cell to inside the cell, and vice versa (in a more limited number of cases. Some receptors change shape when they bind their extra-cellular ligand and this shape change is carried through the trans-membranous domain causing sympathetic shape changes in the cytoplasmic domain (Figure 2) below.
	Figure 2. Signalling molecules (blue spheres) bind the cell surface receptors (pink tube) and induce a conformational change (represented by the shortening of the tubes in the right image compared to the left). These changes in the cytoplasmic domain (lower part of images) can then activate other proteins
Other receptors such as the Epidermal Growth Factor Receptor (EGFR), transduces signals through ligand occupied dimerization and activation by mutual tyrosine phosphorylation.
	Figure 3. Signalling molecules such as EGF (blue spheres) bind the EGF receptor, leading to their dimerization (right image). Once two receptors are coupled they are activated so that their kinase domains in the cytoplasm can phosphorylated the neighbouring receptor. This initiates an intracellular signalling pathway.
In the examples of signal transduction illustrated above the lipid component serves an inhibitory role in that the integrity of the bi-layer "keeps out" the signals. In other types of signalling lipids play an active role in the process and they themselves become signalling molecules. Phospholipids About 50% of the membrane surface is protein (often glycoprotein), the other is lipid. There are many different types of lipid all have fatty acid chains. Lipids such cholesterol affect the fluidity of biological membranes. The main types are the so-called phospholipids (more correctly termed phosphoglycerides, as other lipids contain phosphates). The important property that all lipids have is that they have a hydrophilic "head" and a hydrophobic tail. The tails associate both side to side and end to end spontaneously in water to form bi-layers, the basic structure of all biological membranes.