Authors: Abdur Rub
Here, for the first time we have shown that a single receptor, CD40, by virtue of its re-localization within cholesterol-rich detergent-resistant membrane microdomains (DRMs), can assemble a signalosome able to induce pro-inflammatory mediators and immunity to L. major, while the same receptor excluded from DRMs, as occurs in cholesterol depleted or L. major infected cells, signals IL-10 production and enhanced intracellular growth and lesion progression in BALB/c mice. There is good evidence that these microdomains are platforms for signal transduction. A further example of membrane microdomains is the lateral segregation of glycosphingolipids and cholesterol into liquid-ordered domains. Phase separation of cholesterol-enriched, liquid-ordered domains or lipid rafts has been clearly demonstrated in model membranes and also in biological membranes, although the length and time scales on which this phase separation occurs are a matter of debate. These observations inspired the thought that the lipid raft domain in the membrane is the domain in the liquid ordered phase, and that a strong correlation exists between the molecules recovered in the DRM fraction and those partitioned into raft domains in the membrane. Here we have isolated different signalosomes associated with CD40 in the DRM and non-DRM microdomains regulating the differential cellular responses.
Cholesterol depletion associated with Leishmania major infection alters macrophage CD40 signalosome composition and effector function, Abdur Rub, Ranadhir Dey, Meenakshi Jadhav, Rohan Kamat, Santhosh Chakkaramakkil, Subrata Majumdar, Robin Mukhopadhyaya, and Bhaskar Saha, Nature Immunology 10 (3) 273 - 280 08/02/2009 doi:10.1038/ni.1705
Abdur Rub, National Centre for Cell Science
Source: Protocol Exchange (2009) doi:10.1038/nprot.2009.46. Originally published online 12 February 2009.