STRUCTURE-FUNCTION RELATIONSHIP OF CHOLESTEROL-ENRICHED MEMBRANE MICRODOMAINS

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To study the structure-function relationship of membrane microdomains (lipid rafts) involved in signal transduction, we examined the alterations of lipid rafts in an age-associated decline in T-cell receptor signaling. By analyzing resting and stimulated mouse CD4^+ T cells, we found that the following alterations may be related to the age-dependent decline in T-cell receptor signaling : 1) age-dependent alterations in several lipid raft-associated molecules, and resulting dysregulation of a negative SFK (Src family kinase) regulatory system ; 2) age-associated up-regulation of PD-1-positive T cells that exhibit proliferative hyporesponsiveness; 3) altered localization/topology of cholesterol, one of major constituents of lipid rafts.