Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis

TLDR

Ca²⁺ influx through plasma membrane lesions triggers rapid repair that depends on lysosomal exocytosis, yet how exocytosis leads to membrane resealing, especially for stable pore‑forming lesions, remains unclear. The study aims to determine whether Ca²⁺‑dependent resealing after streptolysin O permeabilization and mechanical wounding requires endocytosis. Endocytosis via a novel pathway removes streptolysin O–containing pores and is similarly essential for repairing mechanically induced lesions. Inhibition of endocytosis impairs repair while its enhancement facilitates resealing, demonstrating that endocytosis promotes wound closure by removing lesions and protecting cells from mechanical injury and pore‑forming toxins. Cell 106:157–169 (2001).

Abstract

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.