TY - JOUR
T1 - Acid sphingomyelinase is required for efficient phago-lysosomal fusion
AU - Schramm, Michael
AU - Herz, Jasmin
AU - Haas, Albert
AU - Krönke, Martin
AU - Utermöhlen, Olaf
PY - 2008
Y1 - 2008
N2 - The acid sphingomyelinase (ASMase) localizes to the lumen of endosomes, phagosomes and lysosomes as well as to the outer leaflet of the plasma membrane and hydrolyses sphingomyelin to ceramide and phosphorylcholine. Using the facultative intracellular bacterium Listeria monocytogenes, we show that maturation of phagosomes into phagolysosomes is severely impaired in macrophages genetically deficient for ASMase. Unlike in wild-type macrophages, phagosomes containing L. monocytogenes in ASMase-/- macrophages remained positive for the late phagosomal markers mannose-6-phosphate receptor (M6PR) and Rab7 for at least 2 h and, correspondingly, showed delayed acquisition of lysosomal markers like lysosome associated membrane protein 1 (Lamp1). The transfer of lysosomal fluid phase markers into phagosomes containing L. monocytogenes was severely impaired in ASMase-/- macrophages and decreased with increasing size of the cargo. Moreover, phagosomes containing L.monocytogenes from ASMase-/- cells acquired significantly less listeriocidal proteases cathepsin D, B and L. The results of this study suggest that ASMase is required for the proper fusion of late phagosomes with lysosomes, which is crucial for efficient transfer of lysosomal antibacterial hydrolases into phagosomes.
AB - The acid sphingomyelinase (ASMase) localizes to the lumen of endosomes, phagosomes and lysosomes as well as to the outer leaflet of the plasma membrane and hydrolyses sphingomyelin to ceramide and phosphorylcholine. Using the facultative intracellular bacterium Listeria monocytogenes, we show that maturation of phagosomes into phagolysosomes is severely impaired in macrophages genetically deficient for ASMase. Unlike in wild-type macrophages, phagosomes containing L. monocytogenes in ASMase-/- macrophages remained positive for the late phagosomal markers mannose-6-phosphate receptor (M6PR) and Rab7 for at least 2 h and, correspondingly, showed delayed acquisition of lysosomal markers like lysosome associated membrane protein 1 (Lamp1). The transfer of lysosomal fluid phase markers into phagosomes containing L. monocytogenes was severely impaired in ASMase-/- macrophages and decreased with increasing size of the cargo. Moreover, phagosomes containing L.monocytogenes from ASMase-/- cells acquired significantly less listeriocidal proteases cathepsin D, B and L. The results of this study suggest that ASMase is required for the proper fusion of late phagosomes with lysosomes, which is crucial for efficient transfer of lysosomal antibacterial hydrolases into phagosomes.
UR - http://www.scopus.com/inward/record.url?scp=48749133600&partnerID=8YFLogxK
U2 - 10.1111/j.1462-5822.2008.01169.x
DO - 10.1111/j.1462-5822.2008.01169.x
M3 - Article
C2 - 18485117
AN - SCOPUS:48749133600
VL - 10
SP - 1839
EP - 1853
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 9
ER -