lipid rafts

Definition: Membrane microdomains that are distinguished from the rest of the plasma membrane by their lipid composition. They usually contain high levels of cholesterol (cholesterol-rich lipid rafts), and gangliosides.

Depending on their function or biochemical characteristics, such as lipid anchoring, proteins are differentially integrated into lipid rafts.

The hypothesis that lipid rafts exist in plasma membranes and have crucial biological functions remains controversial.

The lateral heterogeneity of proteins in the plasma membrane is undisputed, but the contribution of cholesterol-dependent lipid assemblies to this complex, non-random organization promotes vigorous debate.

Membrane microdomains with distinct lipid compositions, called lipid rafts, represent a potential mechanism for compartmentalizing cellular functions within the plane of biological membranes.

SPFH domain-containing proteins are found in lipid raft microdomains in diverse cellular membranes. SPFH proteins have a potential function for in the formation of membrane microdomains and lipid raft-associated processes, such as endocytosis and mechanosensation.

In the liquid disordered matrix of cellular membranes, lateral heterogeneity is induced by ordered platforms forming lipid microdomains.

Biochemically, lipid rafts are characterized by their insolubility in different detergents (e.g. Triton X-100 or CHAPS) at 4 °C. The concept of rafts allows the compartmentalization of membrane processes.

Rafts are involved in modulating cellular structures and cellular function.

Lipid rafts and APP processing

BACE and PSENs are enriched in rafts. ADAM 10, a putative *-secretase, is not present in rafts, supporting the hypothesis that rafts mediate amyloidogenic APP processing.

In this hypothetical model, APP is located in two different pools in the membrane. *-Cleavage might occur outside the detergent-resistant membrane, whereas APP located in rafts is processed by β- and γ-secretases.

References

 Browman DT, Hoegg MB, Robbins SM. The SPFH domain-containing proteins: more than lipid raft markers. Trends Cell Biol. 2007 Aug;17(8):394-402. PMID: 17766116

 Hancock JF. Lipid rafts: contentious only from simplistic standpoints. Nat Rev Mol Cell Biol. 2006 Jun;7(6):456-62. PMID: 16625153