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Article

Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix

1
School of Biology and Ecology, University of Maine, Orono, ME 04469, USA
2
Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA
*
Author to whom correspondence should be addressed.
Current location: St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
Current location: Department of Biological Sciences, King Faisal University, Al Hofuf 31982, Saudi Arabia.
Academic Editors: Rosa Serra and Simon J Conway
J. Dev. Biol. 2021, 9(4), 52; https://doi.org/10.3390/jdb9040052 (registering DOI)
Received: 24 September 2021 / Revised: 5 November 2021 / Accepted: 13 November 2021 / Published: 23 November 2021
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth, and homeostasis is modulation of protein turnover, the balance between synthesis and degradation of muscle proteins. Protein degradation depends upon lysosomal pH, generated and maintained by proton pumps. Sphingolipid transporter 1 (spns1), a highly conserved gene encoding a putative late endosome/lysosome carbohydrate/H+ symporter, plays a pivotal role in maintaining optimal lysosomal pH and spns1−/− mutants undergo premature senescence. However, the impact of dysregulated lysosomal pH on muscle development and homeostasis is not well understood. We found that muscle development proceeds normally in spns1−/− mutants prior to the onset of muscle degeneration. Dysregulation of the extracellular matrix (ECM) at the myotendinous junction (MTJ) coincided with the onset of muscle degeneration in spns1−/− mutants. Expression of the ECM proteins laminin 111 and MMP-9 was upregulated. Upregulation of laminin 111 mitigated the severity of muscle degeneration, as inhibition of adhesion to laminin 111 exacerbated muscle degeneration in spns1−/− mutants. MMP-9 upregulation was induced by tnfsf12 signaling, but abrogation of MMP-9 did not impact muscle degeneration in spns1−/− mutants. Taken together, these data indicate that dysregulated lysosomal pH impacts expression of ECM proteins at the myotendinous junction. View Full-Text
Keywords: zebrafish; spinster; lysosomal myopathy; basement membrane; myotendinous junction; skeletal muscle zebrafish; spinster; lysosomal myopathy; basement membrane; myotendinous junction; skeletal muscle
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MDPI and ACS Style

Coffey, E.C.; Astumian, M.; Alrowaished, S.S.; Schaffer, C.; Henry, C.A. Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix. J. Dev. Biol. 2021, 9, 52. https://doi.org/10.3390/jdb9040052

AMA Style

Coffey EC, Astumian M, Alrowaished SS, Schaffer C, Henry CA. Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix. Journal of Developmental Biology. 2021; 9(4):52. https://doi.org/10.3390/jdb9040052

Chicago/Turabian Style

Coffey, Elizabeth C., Mary Astumian, Sarah S. Alrowaished, Claire Schaffer, and Clarissa A. Henry 2021. "Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix" Journal of Developmental Biology 9, no. 4: 52. https://doi.org/10.3390/jdb9040052

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