|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00621
Research Article |
RI
1 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY
14853, USA
2 Department of Molecular Medicine, Veterinary Medical Center, Cornell
University, Ithaca, NY 14853, USA
Author for correspondence (e-mail:
bab13{at}cornell.edu)
Accepted 15 April 2003
Specialized plasma membrane domains known as lipid rafts participate in
signal transduction and other cellular processes, and their liquid-ordered
properties appear to be important for their function. We investigated the
possibility of using amphiphiles to disrupt lipid rafts and thereby inhibit
IgE-Fc
RI signaling. We find that short-chain ceramides –
C2-ceramide and C6-ceramide – decrease plasma
membrane lipid order and reduce the extent of fluorescence resonance energy
transfer between lipid-raft-associated molecules on intact cells; by contrast,
biologically inactive C2-dihydroceramide does neither. Structural
perturbations by these ceramides parallel their inhibitory effects on
antigen-stimulated Ca2+ mobilization in RBL mast cells in the
presence and absence of extracellular Ca2+. Similar inhibition of
Ca2+ mobilization is caused by n-butanol, which prevents
phosphatidic acid production by phospholipase D, but not by t-butanol, which
does not prevent phosphatidic acid production. These results and previously
reported effects of short-chain ceramides on phospholipase D activity prompted
us to compare the effects of C2-ceramide,
C2-dihydroceramide and C16-ceramide on phospholipase D1
and phospholipase D2 activities in vitro. We find that the effects of these
ceramides on phospholipase D1 activity strongly correlate with their effects
on antigen-stimulated Ca2+ mobilization and with their disruption
of lipid order. Our results indicate that phospholipase D activity is upstream
of antigen-stimulated Ca2+ mobilization in these cells, and they
demonstrate that ceramides can serve as useful probes for investigating roles
of plasma membrane structure and phospholipase D activity in cellular
signaling.
Key words: Ceramides, Lipid rafts, IgE receptors, Phospholipase D, Mast cells
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  R. Efendiev, C. E. Budu, A. M. Bertorello, and C. H. Pedemonte G-protein-coupled Receptor-mediated Traffic of Na,K-ATPase to the Plasma Membrane Requires the Binding of Adaptor Protein 1 to a Tyr-255-based Sequence in the {alpha}-Subunit J. Biol. Chem., June 20, 2008; 283(25): 17561 - 17567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Munday and J. A. Lopez Posttranslational Protein Palmitoylation: Promoting Platelet Purpose Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1496 - 1499. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sengupta, D. Holowka, and B. Baird Fluorescence Resonance Energy Transfer between Lipid Probes Detects Nanoscopic Heterogeneity in the Plasma Membrane of Live Cells Biophys. J., May 15, 2007; 92(10): 3564 - 3574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Preininger, L. G. Henage, W. M. Oldham, E. J. Yoon, H. E. Hamm, and H. A. Brown Direct Modulation of Phospholipase D Activity by Gbeta{gamma} Mol. Pharmacol., July 1, 2006; 70(1): 311 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gosse, A. Wagenknecht-Wiesner, D. Holowka, and B. Baird Transmembrane Sequences Are Determinants of Immunoreceptor Signaling J. Immunol., August 15, 2005; 175(4): 2123 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olivera and J. Rivera Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell J. Immunol., February 1, 2005; 174(3): 1153 - 1158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hitomi, J. Zhang, L. M. Nicoletti, A. C. G. Grodzki, M. C. Jamur, C. Oliver, and R. P. Siraganian Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation Blood, December 15, 2004; 104(13): 4122 - 4128. [Abstract] [Full Text] [PDF]
|
|
