Nature Communications (Jun 2020)
A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction
- Joanne M. Hildebrand,
- Maria Kauppi,
- Ian J. Majewski,
- Zikou Liu,
- Allison J. Cox,
- Sanae Miyake,
- Emma J. Petrie,
- Michael A. Silk,
- Zhixiu Li,
- Maria C. Tanzer,
- Gabriela Brumatti,
- Samuel N. Young,
- Cathrine Hall,
- Sarah E. Garnish,
- Jason Corbin,
- Michael D. Stutz,
- Ladina Di Rago,
- Pradnya Gangatirkar,
- Emma C. Josefsson,
- Kristin Rigbye,
- Holly Anderton,
- James A. Rickard,
- Anne Tripaydonis,
- Julie Sheridan,
- Thomas S. Scerri,
- Victoria E. Jackson,
- Peter E. Czabotar,
- Jian-Guo Zhang,
- Leila Varghese,
- Cody C. Allison,
- Marc Pellegrini,
- Gillian M. Tannahill,
- Esme C. Hatchell,
- Tracy A. Willson,
- Dina Stockwell,
- Carolyn A. de Graaf,
- Janelle Collinge,
- Adrienne Hilton,
- Natasha Silke,
- Sukhdeep K. Spall,
- Diep Chau,
- Vicki Athanasopoulos,
- Donald Metcalf,
- Ronald M. Laxer,
- Alexander G. Bassuk,
- Benjamin W. Darbro,
- Maria A. Fiatarone Singh,
- Nicole Vlahovich,
- David Hughes,
- Maria Kozlovskaia,
- David B. Ascher,
- Klaus Warnatz,
- Nils Venhoff,
- Jens Thiel,
- Christine Biben,
- Stefan Blum,
- John Reveille,
- Michael S. Hildebrand,
- Carola G. Vinuesa,
- Pamela McCombe,
- Matthew A. Brown,
- Benjamin T. Kile,
- Catriona McLean,
- Melanie Bahlo,
- Seth L. Masters,
- Hiroyasu Nakano,
- Polly J. Ferguson,
- James M. Murphy,
- Warren S. Alexander,
- John Silke
Affiliations
- Joanne M. Hildebrand
- The Walter and Eliza Hall Institute of Medical Research
- Maria Kauppi
- The Walter and Eliza Hall Institute of Medical Research
- Ian J. Majewski
- The Walter and Eliza Hall Institute of Medical Research
- Zikou Liu
- The Walter and Eliza Hall Institute of Medical Research
- Allison J. Cox
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine
- Sanae Miyake
- Department of Biochemistry, Toho University School of Medicine, Ota-ku
- Emma J. Petrie
- The Walter and Eliza Hall Institute of Medical Research
- Michael A. Silk
- Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne
- Zhixiu Li
- Translational Genomics Group, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT) at Translational Research Institute
- Maria C. Tanzer
- The Walter and Eliza Hall Institute of Medical Research
- Gabriela Brumatti
- The Walter and Eliza Hall Institute of Medical Research
- Samuel N. Young
- The Walter and Eliza Hall Institute of Medical Research
- Cathrine Hall
- The Walter and Eliza Hall Institute of Medical Research
- Sarah E. Garnish
- The Walter and Eliza Hall Institute of Medical Research
- Jason Corbin
- The Walter and Eliza Hall Institute of Medical Research
- Michael D. Stutz
- The Walter and Eliza Hall Institute of Medical Research
- Ladina Di Rago
- The Walter and Eliza Hall Institute of Medical Research
- Pradnya Gangatirkar
- The Walter and Eliza Hall Institute of Medical Research
- Emma C. Josefsson
- The Walter and Eliza Hall Institute of Medical Research
- Kristin Rigbye
- The Walter and Eliza Hall Institute of Medical Research
- Holly Anderton
- The Walter and Eliza Hall Institute of Medical Research
- James A. Rickard
- The Walter and Eliza Hall Institute of Medical Research
- Anne Tripaydonis
- The Walter and Eliza Hall Institute of Medical Research
- Julie Sheridan
- The Walter and Eliza Hall Institute of Medical Research
- Thomas S. Scerri
- The Walter and Eliza Hall Institute of Medical Research
- Victoria E. Jackson
- The Walter and Eliza Hall Institute of Medical Research
- Peter E. Czabotar
- The Walter and Eliza Hall Institute of Medical Research
- Jian-Guo Zhang
- The Walter and Eliza Hall Institute of Medical Research
- Leila Varghese
- The Walter and Eliza Hall Institute of Medical Research
- Cody C. Allison
- The Walter and Eliza Hall Institute of Medical Research
- Marc Pellegrini
- The Walter and Eliza Hall Institute of Medical Research
- Gillian M. Tannahill
- The Walter and Eliza Hall Institute of Medical Research
- Esme C. Hatchell
- The Walter and Eliza Hall Institute of Medical Research
- Tracy A. Willson
- The Walter and Eliza Hall Institute of Medical Research
- Dina Stockwell
- The Walter and Eliza Hall Institute of Medical Research
- Carolyn A. de Graaf
- The Walter and Eliza Hall Institute of Medical Research
- Janelle Collinge
- The Walter and Eliza Hall Institute of Medical Research
- Adrienne Hilton
- The Walter and Eliza Hall Institute of Medical Research
- Natasha Silke
- The Walter and Eliza Hall Institute of Medical Research
- Sukhdeep K. Spall
- The Walter and Eliza Hall Institute of Medical Research
- Diep Chau
- The Walter and Eliza Hall Institute of Medical Research
- Vicki Athanasopoulos
- Department of Immunology and Infectious Disease and Centre for Personalised Immunology (NHMRC Centre for Research Excellence), John Curtin School of Medical Research, Australian National University
- Donald Metcalf
- The Walter and Eliza Hall Institute of Medical Research
- Ronald M. Laxer
- Division of Rheumatology, The Hospital for Sick Children and the University of Toronto
- Alexander G. Bassuk
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine
- Benjamin W. Darbro
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine
- Maria A. Fiatarone Singh
- Faculty of Health Sciences and Sydney Medical School, University of Sydney
- Nicole Vlahovich
- Department of Sports Medicine, Australian Institute of Sport
- David Hughes
- Department of Sports Medicine, Australian Institute of Sport
- Maria Kozlovskaia
- Department of Sports Medicine, Australian Institute of Sport
- David B. Ascher
- Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne
- Klaus Warnatz
- Department of Internal Medicine, Clinic for Rheumatology and Clinical Immunology, Medical Center –University of Freiburg, Faculty of Medicine
- Nils Venhoff
- Department of Internal Medicine, Clinic for Rheumatology and Clinical Immunology, Medical Center –University of Freiburg, Faculty of Medicine
- Jens Thiel
- Department of Internal Medicine, Clinic for Rheumatology and Clinical Immunology, Medical Center –University of Freiburg, Faculty of Medicine
- Christine Biben
- The Walter and Eliza Hall Institute of Medical Research
- Stefan Blum
- Princess Alexandra Hospital
- John Reveille
- Memorial Hermann Texas Medical Centre
- Michael S. Hildebrand
- Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health
- Carola G. Vinuesa
- Department of Immunology and Infectious Disease and Centre for Personalised Immunology (NHMRC Centre for Research Excellence), John Curtin School of Medical Research, Australian National University
- Pamela McCombe
- The University of Queensland, UQ Centre for Clinical Research, Royal Brisbane & Women’s Hospital
- Matthew A. Brown
- Translational Genomics Group, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT) at Translational Research Institute
- Benjamin T. Kile
- The Walter and Eliza Hall Institute of Medical Research
- Catriona McLean
- Department of Anatomical Pathology, The Alfred Hospital
- Melanie Bahlo
- The Walter and Eliza Hall Institute of Medical Research
- Seth L. Masters
- The Walter and Eliza Hall Institute of Medical Research
- Hiroyasu Nakano
- Department of Biochemistry, Toho University School of Medicine, Ota-ku
- Polly J. Ferguson
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine
- James M. Murphy
- The Walter and Eliza Hall Institute of Medical Research
- Warren S. Alexander
- The Walter and Eliza Hall Institute of Medical Research
- John Silke
- The Walter and Eliza Hall Institute of Medical Research
- DOI
- https://doi.org/10.1038/s41467-020-16819-z
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 16
Abstract
Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.
