Lipid rafts are described as specialized structures, or as dynamic cell membrane microdomains. They are believed to be glycolipoprotein lipid microdomains containing a combination of glycosphingolipids, cholesterol, and protein that is recruited, including receptors. Although initially described in the plasma membrane and Golgi membrane, lipid rafts have also been reported in other endomembranes such as lysosomes. However, it is questionable whether it is appropriate to label any such structures lipid rafts, given that their composition and properties deviate considerably from the original lipid raft theory. The lipid raft theory has a history of being redefined in response to contradictory evidence. Cholesterol is an intrinsic component of the cell membrane where it maintains the stability and fluidity of the membrane. Cholesterol regulates protein signaling as a major organiser of lipid rafts. Lipid rafts serve as organising centers for assembling signalling molecules, and influence membrane protein trafficking, to regulate different cell processes such as neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Some researchers propose that lipid rafts are an incidental feature of only incidental physiological significance.
Properties
One key difference between lipid rafts and the plasma membranes from which they are derived is lipid composition. Research has shown that lipid rafts contain 3 to 5-fold the amount of cholesterol found in the surrounding bilayer. Also, lipid rafts are enriched in sphingolipids such as sphingomyelin, which is typically elevated by 50% compared to the plasma membrane. To offset the elevated sphingolipid levels, phosphatidylcholine levels are decreased which results in similar choline-containing lipid levels between the rafts and the surrounding plasma membrane. Cholesterol interacts preferentially, although not exclusively, with sphingolipids due to their structure and the saturation of the hydrocarbon chains. Although not all of the phospholipids within the raft are fully saturated, the hydrophobic chains of the lipids contained in the rafts are more saturated and tightly packed than the surrounding bilayer. Cholesterol is the dynamic "glue" that holds the raft together. Due to the rigid nature of the sterol group, cholesterol partitions preferentially into the lipid rafts where acyl chains of the lipids tend to be more rigid and in a less fluid state. One important property of membrane lipids is their amphipathic character. Amphipathic lipids have a polar, hydrophilic head group and a non-polar, hydrophobic region. The figure to the right shows the inverted cone-like shape of sphingomyelin and the cone-like shape of cholesterol based on the area of space occupied by the hydrophobic and hydrophilic regions. Cholesterol can pack in between the lipids in rafts, serving as a molecular spacer and filling any voids between associated sphingolipids. Rietveld & Simons related lipid rafts in model membranes to the immiscibility of ordered (Lo phase) and disordered (Ld or Lα phase) liquid phases. The cause of this immiscibility is uncertain, but is thought to minimize the free energy between the two phases. Studies have shown there is a difference in thickness of the lipid rafts and the surrounding membrane which results in hydrophobic mismatch at the boundary between the two phases. This phase height mismatch has been shown to increase line tension which may lead to the formation of larger and more circular raft platforms to minimize the energetic cost of maintaining the rafts as a separate phase. Other spontaneous events, such as curvature of the membrane and fusing of small rafts into larger rafts, can also minimize line tension. By one early definition of lipid rafts, lipid rafts differ from the rest of the plasma membrane. In fact, researchers have hypothesized that the lipid rafts can be extracted from a plasma membrane. The extraction would take advantage of lipid raft resistance to non-ionic detergents, such as Triton X-100 or Brij-98 at low temperatures (e.g., 4 °C). When such a detergent is added to cells, the fluid membrane will dissolve while the lipid rafts may remain intact and could be extracted. Because of their composition and detergent resistance, lipid rafts are also called detergent-insoluble glycolipid-enriched membrane (GEM) complexes or DIGs or Detergent Resistant Membranes (DRMs). However the validity of the detergent resistance methodology of membranes has recently been called into question due to ambiguities in the lipids and proteins recovered and the observation that they can also cause solid areas to form where there were none previously.
Function Mediation of substrate presentation. Lipid rafts localize palmitoylated proteins away from the disordered region of the plasma membrane. Disruption of palmitate mediated localization then allows for exposure of a protein to its binding partner or substrate in the disordered region, an activation mechanism termed substrate presentation. For example, a protein is often palmitoylated and binds phosphatidylinositol 4,5-biphosphate (PIP2). PIP2 is polyunsaturated and does not reside in lipid rafts. When the levels of PIP2 increase in the plasma membrane, the protein trafficks to PIP2 clusters where it can be activated directly by PIP2 (or another molecule that associates with PIP2). It is probable that other functions exist.
… excerpt ends here. Continue reading the full article.
