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An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread.
Tan, Joel M J; Mellouk, Nora; Osborne, Suzanne E; Ammendolia, Dustin A; Dyer, Diana N; Li, Ren; Brunen, Diede; van Rijn, Jorik M; Huang, Ju; Czuczman, Mark A; Cemma, Marija A; Won, Amy M; Yip, Christopher M; Xavier, Ramnik J; MacDuff, Donna A; Reggiori, Fulvio; Debnath, Jayanta; Yoshimori, Tamotsu; Kim, Peter K; Fairn, Gregory D; Coyaud, Etienne; Raught, Brian; Muise, Aleixo M; Higgins, Darren E; Brumell, John H.
Afiliação
  • Tan JMJ; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mellouk N; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Osborne SE; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ammendolia DA; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dyer DN; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Li R; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Brunen D; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • van Rijn JM; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Huang J; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Czuczman MA; Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Cemma MA; Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Won AM; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Yip CM; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Xavier RJ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • MacDuff DA; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Reggiori F; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Debnath J; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
  • Yoshimori T; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
  • Kim PK; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Fairn GD; Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.
  • Coyaud E; Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Raught B; Department of Cell Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Muise AM; Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Higgins DE; Department of Cellular Regulation and Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • Brumell JH; Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
Nat Microbiol ; 3(12): 1472-1485, 2018 12.
Article em En | MEDLINE | ID: mdl-30478389
Plasma membrane integrity is essential for the viability of eukaryotic cells. In response to bacterial pore-forming toxins, disrupted regions of the membrane are rapidly repaired. However, the pathways that mediate plasma membrane repair are unclear. Here we show that autophagy-related (ATG) protein ATG16L1 and its binding partners ATG5 and ATG12 are required for plasma membrane repair through a pathway independent of macroautophagy. ATG16L1 is required for lysosome fusion with the plasma membrane and blebbing responses that promote membrane repair. ATG16L1 deficiency causes accumulation of cholesterol in lysosomes that contributes to defective membrane repair. Cell-to-cell spread by Listeria monocytogenes requires membrane damage by the bacterial toxin listeriolysin O, which is restricted by ATG16L1-dependent membrane repair. Cells harbouring the ATG16L1 T300A allele associated with inflammatory bowel disease were also found to accumulate cholesterol and be defective in repair, linking a common inflammatory disease to plasma membrane integrity. Thus, plasma membrane repair could be an important therapeutic target for the treatment of bacterial infections and inflammatory disorders.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Celular / Proteínas Relacionadas à Autofagia / Listeria monocytogenes Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Celular / Proteínas Relacionadas à Autofagia / Listeria monocytogenes Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article