What are lipid rafts and what purpose do they serve? Despite numerous studies, the existence and exact nature of lipid rafts continue to elude researchers due to the apparent limitations in the methods used in isolating and studying them. However, recent studies indicate that these rafts may play an important role in the compartmentalization of cellular membrane processes and in the development of various diseases.
Basically, lipid rafts are dynamic assemblies of highly ordered microdomains composed mainly of lipids and proteins. While they are mainly located at the outer leaflet of the plasma membrane, they may also be present in other parts of the cells, including the lysosomes and Golgi apparatus. The rafts are rich in cholesterol and sphingolipids (ganglioside 1 or GM1, a commonly used lipid raft marker) and are connected to the inner cytoplasmic leaflet of the lipid bilayer.
In addition, these rafts also contain covalently modified cytoplasmic proteins, glycosyl-phophatidylinositol anchored proteins, and small amounts of phospholipids (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) with side chains that are rich in saturated fatty acids.
Since rafts are extremely small microdomains (with size ranging from 50 to 200 nm) and cannot be directly visualized using a traditional light microscope, researchers rely on their insolubility in non-ionic detergents to isolate them from cellular materials. This explains why they are also known as detergent-resistant membranes.
When researchers tried to overcome this limitation by using fluorescence microscopy or atomic force microscopy, they observed that rafts are more ordered and significantly less fluid than the surrounding bilayer in the lipid-disordered phase. This phase separation is mainly due to the fact that sphingolipids contain saturated fatty acid side chains and that cholesterol and saturated fatty acids are able to pack closer together.
Lipid rafts are involved in many cellular processes such as membrane sorting, trafficking, and cell polarization. And since they contain numerous proteins (e.g., Src family kinases, protein kinase C, growth factor receptors, G proteins, and mitogen-activated protein kinase or MAPK) necessary for signal transduction, they are believed to facilitate the process by bringing the signaling components together through substrate presentation. By exposing the protein to its binding partner in the liquid disordered phase of the lipid bilayer, the interactions can proceed rapidly and more efficiently.
Interestingly, while lipid rafts can initiate signal transduction, they can also terminate the process by preventing the receptors that are located on the cell membrane from binding with the hormones or signaling molecules.
Evidence suggest that lipid rafts are also involved in other signal transduction pathways which may include the following:
- Immunoglobulin E signaling
- T cell antigen receptor signaling
- B cell antigen receptor signaling
- Insulin receptor signaling
- Epidermal growth factor (EGF) signaling
Lipid rafts may also serve as platforms for virus entry. Enveloped viruses such as influenza, Semliki Forest virus (SFV), Sindbis virus (SIN), human T-lymphotropic virus Type 1 (HTLV-1), Ebola virus, Hepatitis B virus, and human herpesvirus 6 (HHV-6) all gain entry to the human body by hijacking the receptors located in the lipid rafts. Non-enveloped virus including the simian virus 40 (SV40) and echovirus type 1 (EV1) can also gain entry by binding with receptors found in the lipid rafts.
Additionally, lipid rafts and raft proteins are implicated in the development of numerous diseases such as Alzheimer’s disease, Parkinson disease, prion diseases, muscular dystrophy, polyneuropathies, autoimmune diseases, atherosclerosis, hypertension, diabetes, osteoarthritis, septic shock, and bacterial infections caused by E. coli, Salmonella, C. tetani, and M. tuberculosis, among others.
While there may be numerous controversies surrounding the topic, the continuing research on lipid rafts may finally help us understand their nature, how they influence the activity of different cell types, and the exact role they play in disease development.