Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis.
Ca2+ influx through plasma membrane lesions triggers a rapid repair process that was previously shown to require the exocytosis of lysosomal organelles (Reddy, A., E. Caler, and N. Andrews. 2001. Cell. 106:157-169). However, how exocytosis leads to membrane resealing has remained obscure, particularly for stable lesions caused by pore-forming proteins. In this study, we show that Ca2+-dependent resealing after permeabilization with the bacterial toxin streptolysin O (SLO) requires endocytosis via a novel pathway that removes SLO-containing pores from the plasma membrane. We also find that endocytosis is similarly required to repair lesions formed in mechanically wounded cells. Inhibition of lesion endocytosis (by sterol depletion) inhibits repair, whereas enhancement of endocytosis through disruption of the actin cytoskeleton facilitates resealing. Thus, endocytosis promotes wound resealing by removing lesions from the plasma membrane. These findings provide an important new insight into how cells protect themselves not only from mechanical injury but also from microbial toxins and pore-forming proteins produced by the immune system.
Idone
Vincent
V
Section of Microbial Pathogenesis and 2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Tam
Christina
C
Goss
John W
JW
Toomre
Derek
D
Pypaert
Marc
M
Andrews
Norma W
NW
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021961:Cell Membrane Structures / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D013261:Sterols / Q000378:metabolism; D013301:Streptolysins / Q000633:toxicity; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology
D001427:Bacterial Toxins; D008565:Membrane Proteins; D013261:Sterols; D013301:Streptolysins; D002118:Calcium