期刊
TRAFFIC
卷 9, 期 10, 页码 1757-1775出版社
WILEY
DOI: 10.1111/j.1600-0854.2008.00800.x
关键词
annexin; apoptosis; calcium; ceramide platform; membrane segregation; raft; sphingolipid
类别
资金
- Swiss National Science Foundation [320000-111778]
- National Research Programme NRP 53 'Musculoskeletal Health-Chronic Pain' [405340-104679/1]
Upon its genesis during apoptosis, ceramide promotes gross reorganization of the plasma membrane structure involving clustering of signalling molecules and an amplification of vesicle formation, fusion and trafficking. The annexins are a family of proteins, which in the presence of Ca2+, bind to membranes containing negatively charged phospholipids. Here, we show that ceramide increases affinity of annexin A1-membrane interaction. In the physiologically relevant range of Ca2+ concentrations, this leads to an increase in the Ca2+ sensitivity of annexin A1-membrane interaction. In fixed cells, using a ceramide-specific antibody, we establish a direct interaction of annexin A1 with areas of the plasma membrane enriched in ceramide (ceramide platforms). In living cells, the intracellular dynamics of annexin A1 match those of plasmalemmal ceramide. Among proteins of the annexin family, the interaction with ceramide platforms is restricted to annexin A1 and is conveyed by its unique N-terminal domain. We demonstrate that intracellular Ca2+ overload occurring at the conditions of cellular stress induces ceramide production. Using fluorescently tagged annexin A1 as a reporter for ceramide platforms and annexin A6 as a non-selective membrane marker, we visualize ceramide platforms for the first time in living cells and provide evidence for a ceramide-driven segregation and internalization of membrane-associated proteins.
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