Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair

Christina Tam, Vincent Idone, Cecilia Devlin, Maria Cecilia Fernandes, Andrew Flannery, Xingxuan He, Edward Schuchman, Ira Tabas, Norma W. Andrews

Research output: Contribution to journalArticlepeer-review

267 Scopus citations

Abstract

Rapid plasma membrane resealing is essential for cellular survival. Earlier studies showed that plasma membrane repair requires Ca2+-dependent exocytosis of lysosomes and a rapid form of endocytosis that removes membrane lesions. However, the functional relationship between lysosomal exocytosis and the rapid endocytosis that follows membrane injury is unknown. In this study, we show that the lysosomal enzyme acid sphingomyelinase (ASM) is released extracellularly when cells are wounded in the presence of Ca2+. ASM-deficient cells, including human cells from Niemann-Pick type A (NPA) patients, undergo lysosomal exocytosis after wounding but are defective in injury-dependent endocytosis and plasma membrane repair. Exogenously added recombinant human ASM restores endocytosis and resealing in ASM-depleted cells, suggesting that conversion of plasma membrane sphingomyelin to ceramide by this lysosomal enzyme promotes lesion internalization. These findings reveal a molecular mechanism for restoration of plasma membrane integrity through exocytosis of lysosomes and identify defective plasma membrane repair as a possible component of the severe pathology observed in NPA patients.

Original languageEnglish
Pages (from-to)1027-1038
Number of pages12
JournalJournal of Cell Biology
Volume189
Issue number6
DOIs
StatePublished - 14 Jun 2010

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