文章基本信息

标题：Defective lysosomal exocytosis and plasma membrane repair in Chediak–Higashi/beige cells
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作者：Chau Huynh ; Doris Roth ; Diane M. Ward 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：48
页码：16795-16800
DOI：10.1073/pnas.0405905101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Plasma membrane resealing is a Ca2+-dependent process that involves the exocytosis of intracellular vesicles next to the wound site. Recent studies revealed that conventional lysosomes behave as Ca2+-regulated secretory compartments and play a central role in membrane resealing. These findings raised the possibility that the complex pathology of lysosomal diseases might also include defects in plasma membrane repair. Here, we investigated the capacity for lysosomal exocytosis and membrane resealing of fibroblasts derived from Chediak-Higashi syndrome (CHS) patients, or from beige-J mice. By using a sensitive electroporation/fluorescence-activated cell sorter-based assay, we show that lysosomal exocytosis triggered by membrane wounding is impaired in both human Chediak-Higashi and mouse beige-J fibroblasts. Lysosomal exocytosis increased when the normal size of lysosomes was restored in beige-J cells by expression of the CHS/Beige protein. A similar effect was seen when the lysosomal enlargement in beige-J cells was reversed by treatment with E64d. In addition, the survival of Chediak-Higashi and beige-J fibroblasts after wounding was reduced, indicating that impaired lysosomal exocytosis inhibits membrane resealing in these mutant cells. Thus, the severe symptoms exhibited by CHS patients may also include defects in the ability of cells to repair plasma membrane lesions.
关键词：lysosome ; injury ; resealing