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Ceramide-rich membrane rafts mediate CD40 clustering.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Jan 01; Vol. 168 (1), pp. 298-307. - Publication Year :
- 2002
-
Abstract
- Many receptor systems use receptor clustering for transmembrane signaling. In this study, we show that acid sphingomyelinase (ASM) is essential for the clustering of CD40. Stimulation of lymphocytes via CD40 ligation results in ASM translocation from intracellular stores, most likely vesicles, into distinct membrane domains on the extracellular surface of the plasma membrane. Surface ASM initiates a release of extracellularly oriented ceramide, which in turn mediates CD40 clustering in sphingolipid-rich membrane domains. ASM, ceramide, and CD40 colocalize in the cap-like structure of stimulated cells. Deficiency of ASM, destruction of sphingolipid-rich rafts, or neutralization of surface ceramide prevents CD40 clustering and CD40-initiated cell signaling. These findings indicate that the ASM-mediated release of ceramide and/or metabolites of ceramide regulate clustering of CD40, which seems to be a prerequisite for cellular activation via CD40.
- Subjects :
- B-Lymphocytes drug effects
Cells, Cultured
Ceramides analysis
Flow Cytometry
Humans
Interleukin-12 biosynthesis
JNK Mitogen-Activated Protein Kinases
Kinetics
MAP Kinase Signaling System
Microscopy, Fluorescence
Mitogen-Activated Protein Kinases metabolism
Protein Transport
Sphingomyelin Phosphodiesterase metabolism
Sphingomyelin Phosphodiesterase pharmacology
B-Lymphocytes immunology
CD40 Antigens metabolism
Ceramides physiology
Lymphocyte Activation
Membrane Microdomains chemistry
Membrane Microdomains physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 168
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 11751974
- Full Text :
- https://doi.org/10.4049/jimmunol.168.1.298