Lipid raft heterogeneity in human peripheral blood T lymphoblasts: a mechanism for regulating the initiation of TCR signal transduction

AE Schade, AD Levine - The Journal of Immunology, 2002 - journals.aai.org
AE Schade, AD Levine
The Journal of Immunology, 2002journals.aai.org
Lateral mobility and spatial organization of proteins within the plasma membrane are likely
to mediate the initial events coordinating T cell activation. Lipid rafts, distinct cholesterol/
sphingolipid-rich membrane microdomains, provide a mechanism for this regulation by
concentrating or excluding signaling proteins. We demonstrate in peripheral blood T cell
lymphoblasts that immediate early phosphotyrosine signal transduction through the TCR
complex is functionally dependent on a distinct population of lipid rafts. Specifically …
Abstract
Lateral mobility and spatial organization of proteins within the plasma membrane are likely to mediate the initial events coordinating T cell activation. Lipid rafts, distinct cholesterol/sphingolipid-rich membrane microdomains, provide a mechanism for this regulation by concentrating or excluding signaling proteins. We demonstrate in peripheral blood T cell lymphoblasts that immediate early phosphotyrosine signal transduction through the TCR complex is functionally dependent on a distinct population of lipid rafts. Specifically, cholesterol extraction destabilizes the membrane microdomains containing Lck, while the rafts containing the adapter protein linker for activation of T cells remain intact. Heterogeneity in the partitioning of these proteins in resting cells was confirmed by immunoelectron microscopy. After T cell activation, both Lck and the linker for activation of T cells colocalize to 50–100 nm microdomains in the plasma membrane, indicating that sequestration of these proteins into distinct lipid rafts may function to regulate the initiation of T cell signal transduction.
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