Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Ronnie Blazev
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Richard J Mills
QIMR Berghofer Medical Research Institute, Brisbane, Australia
Yaan-Kit Ng
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Kevin I Watt
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Daryn Chau
Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, United States
Paul Gregorevic
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia
James BW Hilton
Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia
Leszek Lisowski
Children's Medical Research Institute, University of Sydney, Sydney, Australia; Military Institute of Medicine, Warszawa, Poland
Peixiang Zhang
Department of Human Genetics/Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Karen Reue
Department of Human Genetics/Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Aldons J Lusis
Department of Human Genetics/Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
James E Hudson
QIMR Berghofer Medical Research Institute, Brisbane, Australia
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia; Centre for Muscle Research, University of Melbourne, Melbourne, Australia
Improving muscle function has great potential to improve the quality of life. To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with previously acquired genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis. These data identified thousands of associations between protein abundance and phenotypes and can be accessed online (https://muscle.coffeeprot.com/) to identify regulators of muscle function. We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle. This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show UFMylation is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.
