Journal
JOURNAL OF CELL BIOLOGY
Volume 176, Issue 7, Pages 895-901Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200609149
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Funding
- NHLBI NIH HHS [R24 HL083187, HL-083187] Funding Source: Medline
- NIGMS NIH HHS [GM-222942, R01 GM022942] Funding Source: Medline
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Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveolar endocytosis and beta 1-integrin signaling are stimulated by exogenous glycosphingolipids (GSLs). In this study, we show that a synthetic GSL with nonnatural stereochemistry, beta-D-lactosyl-N-octanoyl-L-threo-sphingosine, (1) selectively inhibits caveolar endocytosis and SV40 virus infection, (2) blocks the clustering of lipids and proteins into GSLs and cholesterol-enriched microdomains (rafts) at the PM, and (3) inhibits beta 1-integrin activation and downstream signaling. Finally, we show that small interfering RNA knockdown of beta 1 integrin in human skin fibroblasts blocks caveolar endocytosis and the stimulation of signaling by a GSL with natural stereochemistry. These experiments identify a new compound that can interfere with biological processes by inhibiting microdomain formation and also identify beta 1 integrin as a potential mediator of signaling by GSLs.
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