TY - JOUR
T1 - Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair
AU - Tam, Christina
AU - Idone, Vincent
AU - Devlin, Cecilia
AU - Fernandes, Maria Cecilia
AU - Flannery, Andrew
AU - He, Xingxuan
AU - Schuchman, Edward
AU - Tabas, Ira
AU - Andrews, Norma W.
PY - 2010/6/14
Y1 - 2010/6/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953576191&partnerID=8YFLogxK
U2 - 10.1083/jcb.201003053
DO - 10.1083/jcb.201003053
M3 - Article
C2 - 20530211
AN - SCOPUS:77953576191
SN - 0021-9525
VL - 189
SP - 1027
EP - 1038
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -