Cells repair holes in their plasma membrane by secreting a lysosomal hydrolase to induce endocytosis, Tam et al. reveal.

If their outer surface is punctured by scraping or by pore-forming bacterial toxins, cells quickly fuse their lysosomes with the plasma membrane, which might provide extra lipids to patch the leak. But puncture repair also involves the removal of damaged plasma membrane by endocytosis. Tam et al. wondered whether the two processes were linked and found that blocking lysosome exocytosis in injured cells prevented endocytosis and plasma membrane repair.

How does lysosome secretion stimulate the internalization of damaged membrane? The endosomes generated during membrane repair look like the vesicles produced by cells exposed to the bacterial enzyme sphingomyelinase, which induces membrane budding by forming ceramide patches on the cell surface. The authors thought that secretion of the lysosomal version of this enzyme, acid sphingomyelinase (ASM), could have a similar effect and found that an ASM inhibitor blocked endocytosis and puncture repair. Cells lacking ASM—including fibroblasts derived from patients with Niemann-Pick disease type A—were also deficient in resealing their membranes after damage, but endocytosis and membrane repair were restored by adding ASM protein to the cells' medium.

Defective membrane repair may therefore contribute to the neurodegenerative pathology of Niemann-Pick type A, which was previously ascribed largely to the intracellular accumulation of sphingomyelin and cholesterol. First author Christina Tam and senior author Norma Andrews now want to determine whether other lysosomal hydrolases stimulate endocytosis and membrane resealing.

et al
J. Cell Biol.