The small chemical vacuolin-1 inhibits Ca2+-dependent lysosomal exocytosis but not cell resealing

被引:123
作者
Cerny, J
Feng, Y
Yu, A
Miyake, K
Borgonovo, B
Klumperman, J
Meldolesi, J
McNeil, PL
Kirchhausen, T [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA
[3] Charles Univ Prague, Dept Physiol Anim & Dev Biol, Prague 2, Czech Republic
[4] Harvard Univ, Sch Med, ICCB, Inst Chem & Cell Biol, Boston, MA 02115 USA
[5] Med Coll Georgia, Dept Anat & Cellular Biol, Augusta, GA 30912 USA
[6] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA
[7] Univ Vita Salute San Raffaele, DIBIT, Dept Neurosci, I-20132 Milan, Italy
[8] San Raffaele Inst, I-20132 Milan, Italy
[9] Univ Med Ctr, Dept Cell Biol, NL-3584 Utrecht, Netherlands
[10] Inst Biomembranes, NL-3584 Utrecht, Netherlands
关键词
chemical genetics; membrane repair; exocytosis;
D O I
10.1038/sj.embor.7400243
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Resealing after wounding, the process of repair following plasma membrane damage, requires exocytosis. Vacuolins are molecules that induce rapid formation of large, swollen structures derived from endosomes and lysosomes by homotypic fusion combined with uncontrolled fusion of the inner and limiting membranes of these organelles. Vacuolin-1, the most potent compound, blocks the Ca2+-dependent exocytosis of lysosomes induced by iono-mycin or plasma membrane wounding, without affecting the process of resealing. In contrast, other cell structures and membrane trafficking functions including exocytosis of enlargeosomes are unaffected. Because cells heal normally in the presence of vacuolin-1, we suggest that lysosomes are dispensable for resealing.
引用
收藏
页码:883 / 888
页数:6
相关论文
共 22 条
[1]   Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship [J].
Andrews, NW .
JOURNAL OF CELL BIOLOGY, 2002, 158 (03) :389-394
[2]   Defective membrane repair in dysferlin-deficient muscular dystrophy [J].
Bansal, D ;
Miyake, K ;
Vogel, SS ;
Groh, S ;
Chen, CC ;
Williamson, R ;
McNeil, PL ;
Campbell, KP .
NATURE, 2003, 423 (6936) :168-172
[3]   Calcium-regulated exocytosis is required for cell membrane resealing [J].
Bi, GQ ;
Alderton, JM ;
Steinhardt, RA .
JOURNAL OF CELL BIOLOGY, 1995, 131 (06) :1747-1758
[4]   Regulated exocytosis: a novel, widely expressed system [J].
Borgonovo, B ;
Cocucci, E ;
Racchetti, G ;
Podini, P ;
Bachi, A ;
Meldolesi, J .
NATURE CELL BIOLOGY, 2002, 4 (12) :955-962
[5]   Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice [J].
Chakrabarti, S ;
Kobayashi, KS ;
Flavell, RA ;
Marks, CB ;
Miyake, K ;
Liston, DR ;
Fowler, KT ;
Gorelick, FS ;
Andrews, NW .
JOURNAL OF CELL BIOLOGY, 2003, 162 (04) :543-549
[6]   Exo1: A new chemical inhibitor of the exocytic pathway [J].
Feng, Y ;
Yu, S ;
Lasell, TKR ;
Jadhav, AP ;
Macia, E ;
Chardin, P ;
Melancon, P ;
Roth, M ;
Mitchison, T ;
Kirchhausen, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (11) :6469-6474
[7]   The biogenesis of multivesicular endosomes [J].
Gruenberg, J ;
Stenmark, H .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (04) :317-323
[8]   Synaptotagmin VII restricts fusion pore expansion during lysosomal exocytosis [J].
Jaiswal, JK ;
Chakrabarti, S ;
Andrews, NW ;
Simon, SM .
PLOS BIOLOGY, 2004, 2 (08) :1224-1232
[9]   Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells [J].
Jaiswal, JK ;
Andrews, NW ;
Simon, SM .
JOURNAL OF CELL BIOLOGY, 2002, 159 (04) :625-635
[10]   Multiple and diverse forms of regulated exocytosis in wild-type and defective PC12 cells [J].
Kasai, H ;
Kishimoto, T ;
Liu, TT ;
Miyashita, Y ;
Podini, P ;
Grohovaz, F ;
Meldolesi, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :945-949