scholarly journals Solving the secretory acid sphingomyelinase puzzle: Insights from lysosome‐mediated parasite invasion and plasma membrane repair

2019 ◽  
Vol 21 (11) ◽  
Author(s):  
Norma W. Andrews
Keyword(s):  
Plasma Membrane ◽  
Acid Sphingomyelinase ◽  
Membrane Repair ◽  
Parasite Invasion ◽  
Plasma Membrane Repair

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

2010 ◽  
Vol 189 (6) ◽  
pp. 1027-1038 ◽  
Author(s):  
Christina Tam ◽  
Vincent Idone ◽  
Cecilia Devlin ◽  
Maria Cecilia Fernandes ◽  
Andrew Flannery ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lysosomal Enzyme ◽  
Membrane Integrity ◽  
Acid Sphingomyelinase ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Cellular Survival ◽  
Plasma Membrane Repair ◽  
Membrane Resealing ◽  
Niemann Pick

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.

scholarly journals Endophilin-A2-dependent tubular endocytosis promotes plasma membrane repair and parasite invasion

2020 ◽  
Vol 134 (5) ◽  
pp. jcs249524
Author(s):  
Matthias Corrotte ◽  
Mark Cerasoli ◽  
Fernando Y. Maeda ◽  
Norma W. Andrews
Keyword(s):  
Plasma Membrane ◽  
Prolonged Exposure ◽  
Alternative Pathway ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Membrane Repair ◽  
Toxin B ◽  
Parasite Invasion ◽  
Caveolin 1 ◽  
Plasma Membrane Repair

ABSTRACTEndocytosis of caveolae has previously been implicated in the repair of plasma membrane wounds. Here, we show that caveolin-1-deficient fibroblasts lacking caveolae upregulate a tubular endocytic pathway and have a reduced capacity to reseal after permeabilization with pore-forming toxins compared with wild-type cells. Silencing endophilin-A2 expression inhibited fission of endocytic tubules and further reduced plasma membrane repair in cells lacking caveolin-1, supporting a role for tubular endocytosis as an alternative pathway for the removal of membrane lesions. Endophilin-A2 was visualized in association with cholera toxin B-containing endosomes and was recruited to recently formed intracellular vacuoles containing Trypanosoma cruzi, a parasite that utilizes the plasma membrane wounding repair pathway to invade host cells. Endophilin-A2 deficiency inhibited T. cruzi invasion, and fibroblasts deficient in both caveolin-1 and endophilin-A2 did not survive prolonged exposure to the parasites. These findings reveal a novel crosstalk between caveolin-1 and endophilin-A2 in the regulation of clathrin-independent endocytosis and plasma membrane repair, a process that is subverted by T. cruzi parasites for cell invasion.

scholarly journals Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

2011 ◽  
Vol 208 (5) ◽  
pp. 909-921 ◽  
Author(s):  
Maria Cecilia Fernandes ◽  
Mauro Cortez ◽  
Andrew R. Flannery ◽  
Christina Tam ◽  
Renato A. Mortara ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Invasion ◽  
Acid Sphingomyelinase ◽  
Host Cells ◽  
Cell Contact ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Plasma Membrane Repair

Upon host cell contact, the protozoan parasite Trypanosoma cruzi triggers cytosolic Ca2+ transients that induce exocytosis of lysosomes, a process required for cell invasion. However, the exact mechanism by which lysosomal exocytosis mediates T. cruzi internalization remains unclear. We show that host cell entry by T. cruzi mimics a process of plasma membrane injury and repair that involves Ca2+-dependent exocytosis of lysosomes, delivery of acid sphingomyelinase (ASM) to the outer leaflet of the plasma membrane, and a rapid form of endocytosis that internalizes membrane lesions. Host cells incubated with T. cruzi trypomastigotes are transiently wounded, show increased levels of endocytosis, and become more susceptible to infection when injured with pore-forming toxins. Inhibition or depletion of lysosomal ASM, which blocks plasma membrane repair, markedly reduces the susceptibility of host cells to T. cruzi invasion. Notably, extracellular addition of sphingomyelinase stimulates host cell endocytosis, enhances T. cruzi invasion, and restores normal invasion levels in ASM-depleted cells. Ceramide, the product of sphingomyelin hydrolysis, is detected in newly formed parasitophorous vacuoles containing trypomastigotes but not in the few parasite-containing vacuoles formed in ASM-depleted cells. Thus, T. cruzi subverts the ASM-dependent ceramide-enriched endosomes that function in plasma membrane repair to infect host cells.

scholarly journals Plasma membrane repairs by small GTPase Rab3a

2016 ◽  
Vol 213 (6) ◽  
pp. 613-615 ◽  
Author(s):  
Camilla Raiborg ◽  
Harald Stenmark
Keyword(s):  
Plasma Membrane ◽  
Small Gtpase ◽  
Membrane Repair ◽  
Cell Biol ◽  
Plasma Membrane Repair

Lysosomes fuse with the plasma membrane to help repair membrane lesions, but how they are positioned close to these lesions is not fully understood. Now, Encarnação et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511093) demonstrate that the lysosomal GTPase Rab3a and its effectors orchestrate lysosome positioning and plasma membrane repair.

scholarly journals Mitochondrial fragmentation enables localized signaling required for cell repair

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Adam Horn ◽  
Shreya Raavicharla ◽  
Sonna Shah ◽  
Dan Cox ◽  
Jyoti K. Jaiswal
Keyword(s):  
Plasma Membrane ◽  
Calcium Influx ◽  
Cell Damage ◽  
Mitochondrial Fission ◽  
Adaptor Protein ◽  
Mitochondrial Fragmentation ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Mitochondrial Signaling ◽  
Plasma Membrane Repair

Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.

scholarly journals Annexin A7 is required for ESCRT III-mediated plasma membrane repair

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stine Lauritzen Sønder ◽  
Theresa Louise Boye ◽  
Regine Tölle ◽  
Jörn Dengjel ◽  
Kenji Maeda ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Repair ◽  
Plasma Membrane Repair ◽  
Annexin A7

Plasma membrane repair and cellular damage control: The annexin survival kit

2011 ◽  
Vol 81 (6) ◽  
pp. 703-712 ◽  
Author(s):  
Annette Draeger ◽  
Katia Monastyrskaya ◽  
Eduard B. Babiychuk
Keyword(s):  
Plasma Membrane ◽  
Damage Control ◽  
Cellular Damage ◽  
Membrane Repair ◽  
Plasma Membrane Repair

An actin-dependent annexin complex mediates plasma membrane repair in muscle

2016 ◽  
Vol 213 (7) ◽  
pp. 2137OIA58 ◽  
Author(s):  
Alexis R. Demonbreun ◽  
Mattia Quattrocelli ◽  
David Y. Barefield ◽  
Madison V. Allen ◽  
Kaitlin E. Swanson ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Repair ◽  
Plasma Membrane Repair
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