Caveolae internalization repairs wounded cells and muscle fibers
Matthias Corrotte,
Patricia E Almeida,
Christina Tam,
Thiago Castro-Gomes,
Maria Cecilia Fernandes,
Bryan A Millis,
Mauro Cortez,
Heather Miller,
Wenxia Song,
Timothy K Maugel,
Norma W Andrews
Affiliations
Matthias Corrotte
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Patricia E Almeida
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States; CAPES Foundation, Brazil Ministry of Education, Brasilia, Brazil
Christina Tam
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Thiago Castro-Gomes
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Maria Cecilia Fernandes
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Bryan A Millis
Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Mauro Cortez
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Heather Miller
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Wenxia Song
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
Timothy K Maugel
Laboratory for Biological Ultrastructure, University of Maryland, College Park, United States
Norma W Andrews
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
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 Ca2+-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.
