Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix.
Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix.
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溶酶体功能影响骨骼肌细胞外基质。
DOI：
10.3390/jdb9040052
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发表时间：
2021-11-23
影响因子：
2.7
通讯作者：
Henry CA
中科院分区：
文献类型：
--
作者：
Coffey EC;Astumian M;Alrowaished SS;Schaffer C;Henry CA
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.
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影响因子：
4.6
作者：
Brkic M;Balusu S;Libert C;Vandenbroucke RE
通讯作者：
Vandenbroucke RE
影响因子：
64.8
作者：
Graves, Austin R.;Curran, Patricia K.;Mindell, Joseph A.
通讯作者：
Mindell, Joseph A.
影响因子：
3.5
作者：
Carmignac, Virginie;Svensson, Martina;Durbeej, Madeleine
通讯作者：
Durbeej, Madeleine
影响因子：
2.7
作者：
Goody, Michelle F.;Sher, Roger B.;Henry, Clarissa A.
通讯作者：
Henry, Clarissa A.
影响因子：
2.7
作者：
Jessen, Jason R.
通讯作者：
Jessen, Jason R.