Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.
Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.
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DOI：
10.1098/rsob.160211
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发表时间：
2016-09
期刊：
影响因子：
5.8
通讯作者：
Maftah A
中科院分区：
文献类型：
--
作者：
Al Jaam B;Heu K;Pennarubia F;Segelle A;Magnol L;Germot A;Legardinier S;Blanquet V;Maftah A
出生后骨骼肌的生长是由于卫星细胞的激活和/或蛋白质合成的增加。Notch信号通路维持卫星细胞处于静止状态，并且一旦激活，维持它们的增殖和向分化的承诺。在哺乳动物中，POFUT 1介导的O-岩藻糖基化调节NOTCH受体与DELTA/JAGGED家族配体之间的相互作用，从而启动经典Notch信号传导的激活。在这里，我们分析了Pofut 1基因表达下调对突变Pofut 1cax/cax（cax，紧凑的轴向骨骼）小鼠的出生后肌肉生长及其卫星细胞衍生的成肌细胞（SCDM）的分化的后果。与野生型C3 H小鼠相比，Pofut 1cax/cax小鼠表现出肌肉肥大，无增生和卫星细胞数量减少。与这些观察结果一致，Pofut 1cax/cax SCDM分化较早，同时Pax 7表达减少，PAX 7 +/MYOD−祖细胞减少。体外结合测定显示，DELTA-LIKE 1配体（DLL 1）与在SCDM的细胞表面表达的Notch受体的相互作用减少，导致Notch信号传导减少，如通过切割的NICD和Notch靶基因的定量所见。这些结果表明，POFUT 1介导的NOTCH受体的O-岩藻糖基化调节小鼠的肌源性细胞分化并影响出生后肌肉生长。
Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1cax/cax (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1cax/cax mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1cax/cax SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7+/MYOD− progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.
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影响因子：
10.5
作者：
Kassar-Duchossoy, L;Giacone, E;Tajbakhsh, S
通讯作者：
Tajbakhsh, S
影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
影响因子：
4.8
作者：
Harvey, Beth M.;Rana, Nadia A.;Haltiwanger, Robert S.
通讯作者：
Haltiwanger, Robert S.
DOI：
10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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