The proteomic profile of the human myotendinous junction
Anders Karlsen,
Alba Gonzalez-Franquesa,
Jens R. Jakobsen,
Michael R. Krogsgaard,
Manuel Koch,
Michael Kjaer,
Stefano Schiaffino,
Abigail L. Mackey,
Atul S. Deshmukh
Affiliations
Anders Karlsen
Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Denmark and Part of IOC Research Center, Copenhagen, Denmark; Center for Healthy Aging, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Alba Gonzalez-Franquesa
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Jens R. Jakobsen
Section for Sports Traumatology M51, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Denmark and Part of IOC Research Center, Copenhagen, Denmark
Michael R. Krogsgaard
Section for Sports Traumatology M51, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Denmark and Part of IOC Research Center, Copenhagen, Denmark
Manuel Koch
Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Michael Kjaer
Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Denmark and Part of IOC Research Center, Copenhagen, Denmark; Center for Healthy Aging, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Stefano Schiaffino
Venetian Institute of Molecular Medicine (VIMM), Padova, Italy
Abigail L. Mackey
Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Denmark and Part of IOC Research Center, Copenhagen, Denmark; Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Corresponding author
Atul S. Deshmukh
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark; Corresponding author
Summary: Proteomics analysis of skeletal muscle has recently progressed from whole muscle tissue to single myofibers. Here, we further focus on a specific myofiber domain crucial for force transmission from muscle to tendon, the myotendinous junction (MTJ). To overcome the anatomical constraints preventing the isolation of pure MTJs, we performed in-depth analysis of the MTJ by progressive removal of the muscle component in semitendinosus muscle-tendon samples. Using detergents with increasing stringency, we quantified >3000 proteins across all samples, and identified 112 significantly enriched MTJ proteins, including 24 known MTJ-enriched proteins. Of the 88 novel MTJ markers, immunofluorescence analysis confirmed the presence of tetraspanin-24 (CD151), kindlin-2 (FERMT2), cartilage intermediate layer protein 1 (CILP), and integrin-alpha10 (ITGA10), at the human MTJ. Together, these human data constitute the first detailed MTJ proteomics resource that will contribute to advance understanding of the biology of the MTJ and its failure in pathological conditions.
