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Title: Lipid rafts regulate cellular CD40 receptor localization in vascular endothelial cells

Abstract

Cholesterol enriched lipid rafts are considered to function as platforms involved in the regulation of membrane receptor signaling complex through the clustering of signaling molecules. In this study, we tested whether these specialized membrane microdomains affect CD40 localization in vitro and in vivo. Here, we provide evidence that upon CD40 ligand stimulation, endogenous and exogenous CD40 receptor is rapidly mobilized into lipid rafts compared with unstimulated HAECs. Efficient binding between CD40L and CD40 receptor also increases amounts of CD40 protein levels in lipid rafts. Deficiency of intracellular conserved C terminus of the CD40 cytoplasmic tail impairs CD40 partitioning in raft. Raft disorganization after methyl-{beta}-cyclodextrin treatment diminishes CD40 localization into rafts. In vivo studies show that elevation of circulating cholesterol in high-cholesterol fed rabbits increases the cholesterol content and CD40 receptor localization in lipid rafts. These findings identify a physiological role for membrane lipid rafts as a critical regulator of CD40-mediated signal transduction and raise the possibility that certain pathologic conditions may be treated by altering CD40 signaling with drugs affecting its raft localization.

Authors:
; ; ; ; ; ;  [1]
  1. Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), 74 Zhongshan Road 2, Guangzhou, Guangdong Province 510080 (China)
Publication Date:
OSTI Identifier:
21032903
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 361; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2007.07.102; PII: S0006-291X(07)01575-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHOLESTEROL; DRUGS; GENE REGULATION; IN VITRO; IN VIVO; LIGANDS; LIPIDS; MEMBRANES; MOLECULES; RABBITS; RECEPTORS

Citation Formats

Min, Xia, Qing, Wang, Huilian, Zhu, Jing, Ma, Mengjun, Hou, Zhihong, Tang, Juanjuan, Li, and Ling Wenhua. Lipid rafts regulate cellular CD40 receptor localization in vascular endothelial cells. United States: N. p., 2007. Web.
Min, Xia, Qing, Wang, Huilian, Zhu, Jing, Ma, Mengjun, Hou, Zhihong, Tang, Juanjuan, Li, & Ling Wenhua. Lipid rafts regulate cellular CD40 receptor localization in vascular endothelial cells. United States.
Min, Xia, Qing, Wang, Huilian, Zhu, Jing, Ma, Mengjun, Hou, Zhihong, Tang, Juanjuan, Li, and Ling Wenhua. Fri . "Lipid rafts regulate cellular CD40 receptor localization in vascular endothelial cells". United States.
@article{osti_21032903,
title = {Lipid rafts regulate cellular CD40 receptor localization in vascular endothelial cells},
author = {Min, Xia and Qing, Wang and Huilian, Zhu and Jing, Ma and Mengjun, Hou and Zhihong, Tang and Juanjuan, Li and Ling Wenhua},
abstractNote = {Cholesterol enriched lipid rafts are considered to function as platforms involved in the regulation of membrane receptor signaling complex through the clustering of signaling molecules. In this study, we tested whether these specialized membrane microdomains affect CD40 localization in vitro and in vivo. Here, we provide evidence that upon CD40 ligand stimulation, endogenous and exogenous CD40 receptor is rapidly mobilized into lipid rafts compared with unstimulated HAECs. Efficient binding between CD40L and CD40 receptor also increases amounts of CD40 protein levels in lipid rafts. Deficiency of intracellular conserved C terminus of the CD40 cytoplasmic tail impairs CD40 partitioning in raft. Raft disorganization after methyl-{beta}-cyclodextrin treatment diminishes CD40 localization into rafts. In vivo studies show that elevation of circulating cholesterol in high-cholesterol fed rabbits increases the cholesterol content and CD40 receptor localization in lipid rafts. These findings identify a physiological role for membrane lipid rafts as a critical regulator of CD40-mediated signal transduction and raise the possibility that certain pathologic conditions may be treated by altering CD40 signaling with drugs affecting its raft localization.},
doi = {},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 361,
place = {United States},
year = {2007},
month = {9}
}