γ-sarcoglycan deficiency increases cell contractility, apoptosis and MAPK pathway activation but does not affect adhesion
γ-sarcoglycan deficiency increases cell contractility, apoptosis and MAPK pathway activation but does not affect adhesion
复制标题
DOI：
10.1242/jcs.01717
复制
发表时间：
2005-04-01
影响因子：
4
通讯作者：
Discher, DE
中科院分区：
文献类型：
--
作者：
Griffin, MA;Feng, HS;Discher, DE
γ-肌聚糖（γ SG）在正常肌管中的功能在很大程度上是未知的，然而，已知γ SG与肌营养不良蛋白聚糖组装成关键的膜复合物，并且其缺陷是肢带型肌营养不良症的一个已知原因。以前的研究结果从γ SG缺陷小鼠的细胞凋亡在这里扩展到细胞培养，其中细胞凋亡被认为是增加超过十倍，在γ SG缺陷的肌管相比，正常细胞。缺陷的肌管还表现出增加的收缩预应力，当细胞轻微分离或自分离时，其导致更大的缩短和加宽。然而，单肌管的微量移液器强制剥离显示细胞粘附没有显着差异。与更多的收缩表型一致，肌动蛋白肌球蛋白条纹在γ SG缺陷肌管中比在正常细胞中更突出。超过12个信号蛋白的初始磷筛选揭示了正常和γ SG（-/-）肌肉之间的许多差异，无论是之前还是之后的拉伸。MAPK通路蛋白的活化变化最大，尽管其他与高血压相关的蛋白也出现了显著的磷酸化。我们的结论是，γ SG正常缓和收缩应力骨骼肌，我们提出了一个角色，γ SG在膜为基础的信号传导的影响，预应力和sarcomerogenesis。
The functions of gamma-sarcoglycan (gamma SG) in normal myotubes are largely unknown, however gamma SG is known to assemble into a key membrane complex with dystroglycan and its deficiency is one known cause of limb-girdle muscular dystrophy. Previous findings of apoptosis from gamma SG-deficient mice are extended here to cell culture where apoptosis is seen to increase more than tenfold in gamma SG-deficient myotubes compared with normal cells. The deficient myotubes also exhibit an increased contractile prestress that results in greater shortening and widening when the cells are either lightly detached or self-detached. However, micropipette-forced peeling of single myotubes revealed no significant difference in cell adhesion. Consistent with a more contractile phenotype, acto-myosin striations were more prominent in gamma SG-deficient myotubes than in normal cells. An initial phosphoscreen of more than 12 signaling proteins revealed a number of differences between normal and gamma SG(-/-) muscle, both before and after stretching. MAPK-pathway proteins displayed the largest changes in activation, although significant phosphorylation also appeared for other proteins linked to hypertension. We conclude that gamma SG normally moderates contractile prestress in skeletal muscle, and we propose a role for gamma SG in membrane-based signaling of the effects of prestress and sarcomerogenesis.