In Vivo Imaging of Molecular Interactions at Damaged Sarcolemma
In Vivo Imaging of Molecular Interactions at Damaged Sarcolemma
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DOI：
10.1016/j.devcel.2011.12.008
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发表时间：
2012-03-13
影响因子：
11.8
通讯作者：
Straehle, Uwe
中科院分区：
文献类型：
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作者：
Roostalu, Urmas;Straehle, Uwe
肌细胞具有显著的修复质膜损伤的能力。已知dysferlin（染料）突变可引起人类进行性肌病，可能是由于肌膜修复受损。我们在这里表明，Dysf和膜联蛋白A6（Anxa 6）功能的丧失导致斑马鱼肌病。通过使用高分辨率成像的肌纤维在完整的动物，我们揭示了连续阶段的肌膜修复。最初，富含Dysf的膜囊泡与细胞质Anxa 6一起在病变处相互独立地形成紧密的补丁。在随后的步骤中，膜联蛋白A2 a（Anxa 2a）随后是膜联蛋白A1 a（Anxa 1a）在斑块处积累;这些膜联蛋白的募集依赖于Dysf和Anxa 6。因此，肌膜修复依赖于蛋白质-膜支架的有序组装。此外，我们还提供了几条证据，证明肌膜修复的膜来源于一种专门的质膜复合物。
Muscle cells have a remarkable capability to repair plasma membrane lesions. Mutations in dysferlin (dye) are known to elicit a progressive myopathy in humans, probably due to impaired sarcolemmal repair. We show here that loss of Dysf and annexin A6 (Anxa6) function lead to myopathy in zebrafish. By use of high-resolution imaging of myofibers in intact animals, we reveal sequential phases in sarcolemmal repair. Initially, membrane vesicles enriched in Dysf together with cytoplasmic Anxa6 form a tight patch at the lesion independently of one another. In the subsequent steps, annexin A2a (Anxa2a) followed by annexin A1a (Anxa1a) accumulate at the patch; the recruitment of these annexins depends on Dysf and Anxa6. Thus, sarcolemmal repair relies on the ordered assembly of a protein-membrane scaffold. Moreover, we provide several lines of evidence that the membrane for sarcolemmal repair is derived from a specialized plasma membrane co,partment.