Defective lysosomal exocytosis and plasma membrane repair in Chediak–Higashi/beige cells

Proceedings of the National Academy of Sciences of the United States of America - Tập 101 Số 48 - Trang 16795-16800 - 2004
Chau Huynh1, Doris Roth1,2, Diane M. Ward3,1, Jerry Kaplan3,1, Norma W. Andrews1
1Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536; and Department of Pathology, University of Utah, Salt Lake City, UT 84132
2Swiss Federal Institute of Technology, Zurich
3MICROBIOLOGY & IMMUNOLOGY

Tóm tắt

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 frombeige-Jmice. 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 mousebeige-Jfibroblasts. Lysosomal exocytosis increased when the normal size of lysosomes was restored inbeige-Jcells by expression of the CHS/Beige protein. A similar effect was seen when the lysosomal enlargement inbeige-Jcells was reversed by treatment with E64d. In addition, the survival of Chediak–Higashi andbeige-Jfibroblasts 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.

Từ khóa


Tài liệu tham khảo

10.1034/j.1600-0749.2002.02038.x

10.1034/j.1600-0854.2000.011102.x

10.1074/jbc.272.47.29790

10.1084/jem.151.5.1039

10.1084/jem.151.5.1049

10.1182/blood.V85.11.3328.bloodjournal85113328

10.1007/BF00305881

10.1016/S0962-8924(00)01794-3

10.1083/jcb.137.1.93

10.1074/jbc.M400798200

10.1083/jcb.148.6.1141

10.1083/jcb.200305131

10.1016/S0092-8674(01)00421-4

10.1038/ng0796-303

10.1016/0022-1759(83)90303-4

10.1016/0003-2697(91)90168-S

10.1093/nar/15.3.1311

10.1016/0005-2736(77)90252-8

10.1007/BF01233251

10.1034/j.1600-0854.2003.00093.x

10.1002/jlb.67.5.749

10.1083/jcb.137.1.1

10.1083/jcb.200208154

Jaiswal, J. K., Chakrabarti, S., Andrews, N. W. & Simon, S. M. (2004) PLoS Biol. 2, 1224–1232.

10.1103/PhysRevE.66.052901

10.1038/jid.1968.2

10.1111/j.1600-0749.1998.tb00713.x

Baetz, K., Isaaz, S. & Griffiths, G. M. (1995) J. Immunol. 154, 6122–6131.7751653

10.1083/jcb.141.5.1121

Lem, L., Riethof, D. A., Scidmore-Carlson, M., Griffiths, G. M., Hackstadt, T. & Brodsky, F. M. (1999) J. Immunol. 162, 523–532.9886429

10.1083/jcb.67.3.774

Uchino, M., Uyama, E., Hirano, T., Nakamura, T., Fukushima, T. & Ando, M. (1993) Acta Neuropathol. 86, 521–524.8310803

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 101 Số 48

16795-16800

Thông tin tác giả