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Commun Biol. 2019 May 9;2:178. doi: 10.1038/s42003-019-0405-7. eCollection 2019.

Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.

Author information

1
1Division of Cardiology, School of Medicine, University of California, San Diego, 92093 CA USA.
2
2Department of Orthopedic Surgery, School of Medicine, University of California, San Diego, 92093 CA USA.
3
3Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena, Siena, 53100 Italy.
4
Université Grenoble Alpes, HP2, Grenoble, 38706 France.
5
5Department of Chemistry and Biochemistry, University of California, San Diego, 92093 CA USA.
6
6Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, 413 45 Sweden.
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Contributed equally

Abstract

Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, uncovering additional changes to the muscle metabolism. Our analyses suggest that all obscurin protein family members play functions for muscle membrane systems.

KEYWORDS:

Experimental models of disease; Mechanisms of disease; Membrane proteins; Molecular medicine

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