Caveolae internalization repairs wounded cells and muscle fibers.
Rapid repair of plasma membrane wounds is critical for cellular survival. Muscle fibers are particularly susceptible to injury, and defective sarcolemma resealing causes muscular dystrophy. Caveolae accumulate in dystrophic muscle fibers and caveolin and cavin mutations cause muscle pathology, but the underlying mechanism is unknown. Here we show that muscle fibers and other cell types repair membrane wounds by a mechanism involving Ca(2+)-triggered exocytosis of lysosomes, release of acid sphingomyelinase, and rapid lesion removal by caveolar endocytosis. Wounding or exposure to sphingomyelinase triggered endocytosis and intracellular accumulation of caveolar vesicles, which gradually merged into larger compartments. The pore-forming toxin SLO was directly visualized entering cells within caveolar vesicles, and depletion of caveolin inhibited plasma membrane resealing. Our findings directly link lesion removal by caveolar endocytosis to the maintenance of plasma membrane and muscle fiber integrity, providing a mechanistic explanation for the muscle pathology associated with mutations in caveolae proteins. DOI:http://dx.doi.org/10.7554/eLife.00926.001.
Department of Cell Biology and Molecular Genetics , University of Maryland , College Park , United States.
Matthias
M
Corrotte
Patricia E
PE
Almeida
Christina
C
Tam
Thiago
T
Castro-Gomes
Maria Cecilia
MC
Fernandes
Bryan A
BA
Millis
Mauro
M
Cortez
Heather
H
Miller
Wenxia
W
Song
Timothy K
TK
Maugel
Norma W
NW
Andrews
D002118:Calcium / Q000378:metabolism; D021941:Caveolae / Q000502:physiology*; D002470:Cell Survival; D002518:Ceramides / Q000378:metabolism; D005089:Exocytosis; D010539:Permeability; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014945:Wound Healing
D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase; D002118:Calcium
Human; Mouse; endocytosis; lysosome; toxin