Nature Communications (Dec 2019)
Muscleblind acts as a modifier of FUS toxicity by modulating stress granule dynamics and SMN localization
- Ian Casci,
- Karthik Krishnamurthy,
- Sukhleen Kour,
- Vadreenath Tripathy,
- Nandini Ramesh,
- Eric N. Anderson,
- Lara Marrone,
- Rogan A. Grant,
- Stacie Oliver,
- Lauren Gochenaur,
- Krishani Patel,
- Jared Sterneckert,
- Amanda M. Gleixner,
- Christopher J. Donnelly,
- Marc-David Ruepp,
- Antonella M. Sini,
- Emanuela Zuccaro,
- Maria Pennuto,
- Piera Pasinelli,
- Udai Bhan Pandey
Affiliations
- Ian Casci
- Department of Human Genetics, University of Pittsburgh Graduate School of Public Health
- Karthik Krishnamurthy
- Department of Neuroscience, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Jefferson University
- Sukhleen Kour
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Vadreenath Tripathy
- Center for Regenerative Therapies TU Dresden, Technische Universität Dresden, Fetscherstr. 105
- Nandini Ramesh
- Department of Human Genetics, University of Pittsburgh Graduate School of Public Health
- Eric N. Anderson
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Lara Marrone
- Center for Regenerative Therapies TU Dresden, Technische Universität Dresden, Fetscherstr. 105
- Rogan A. Grant
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Stacie Oliver
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Lauren Gochenaur
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Krishani Patel
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Jared Sterneckert
- Center for Regenerative Therapies TU Dresden, Technische Universität Dresden, Fetscherstr. 105
- Amanda M. Gleixner
- Department of Neurobiology, School of Medicine, University of Pittsburgh
- Christopher J. Donnelly
- Department of Neurobiology, School of Medicine, University of Pittsburgh
- Marc-David Ruepp
- UK Dementia Research Institute at King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London
- Antonella M. Sini
- Department of Biomedical Sciences (DBS), University of Padova
- Emanuela Zuccaro
- Department of Biomedical Sciences (DBS), University of Padova
- Maria Pennuto
- Department of Biomedical Sciences (DBS), University of Padova
- Piera Pasinelli
- Department of Neuroscience, Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Jefferson University
- Udai Bhan Pandey
- Department of Human Genetics, University of Pittsburgh Graduate School of Public Health
- DOI
- https://doi.org/10.1038/s41467-019-13383-z
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 20
Abstract
The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.
