近日,，卡爾斯魯厄理工學(xué)院和海德堡大學(xué)的研究人員使用了一種新穎的高分辨率成像方法，首次成功地實時觀察活體中細(xì)胞膜的修復(fù)過程,，研究結(jié)果有助于人類肌肉疾病治療的發(fā)展以及為生物技術(shù)開發(fā)出更多發(fā)展?jié)摿Γ嚓P(guān)研究成果刊登在了國際雜志Developmental Cell上,。
每個細(xì)胞都由薄的脂質(zhì)雙層所包圍,，從而隔離開細(xì)胞獨(dú)特的內(nèi)環(huán)境與細(xì)胞外環(huán)境。破壞脂質(zhì)雙層也就是細(xì)胞膜會破壞細(xì)胞功能,，甚至可能導(dǎo)致細(xì)胞的死亡,。舉例來說，走下坡路會使我們腿部肌肉細(xì)胞的細(xì)胞膜出現(xiàn)許多小孔,。為了避免不可修復(fù)的傷害,，肌肉細(xì)胞有高效的系統(tǒng)可以再次密封這些小孔。
Uwe Strähle和Urmas Roostalu博士使用了一種新穎的高分辨率成像方法,，首次實時觀察了活體動物的細(xì)胞膜修復(fù)過程,。他們用熒光蛋白標(biāo)記了斑馬魚幼體肌肉組織的修復(fù)蛋白。研究人員用激光照射肌肉細(xì)胞的細(xì)胞膜并燒出一些小孔,，然后在顯微鏡下實時地觀察這些小孔的修復(fù)過程,。觀察發(fā)現(xiàn)膜小泡和兩種蛋白質(zhì)Dysferlin和膜聯(lián)蛋白A6快速地形成修復(fù)補(bǔ)丁。其他的膜聯(lián)蛋白隨后積聚在受傷的細(xì)胞膜處,?？査刽敹蚝秃５聽柋さ难芯咳藛T發(fā)現(xiàn)，細(xì)胞從內(nèi)部積聚了多層修復(fù)補(bǔ)丁在細(xì)胞外壞境中密封細(xì)胞內(nèi)部,。此外,，研究人員還發(fā)現(xiàn)存在一個特定的細(xì)胞膜區(qū)域，可以快速地為細(xì)胞膜提供修復(fù)膜上小孔的物質(zhì),。
膜修復(fù)的動物模型會繼續(xù)確定在密封過程新的蛋白質(zhì),，并且?guī)椭U明這其中的機(jī)理。研究結(jié)果有助于人類肌肉疾病治療的發(fā)展以及為生物技術(shù)開發(fā)出更多發(fā)展?jié)摿?。（生物谷Bioon.com）
doi:10.1016/j.devcel.2011.12.008
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In Vivo Imaging of Molecular Interactions at Damaged Sarcolemma
Urmas Roostalu, Uwe Strähle
Muscle cells have a remarkable capability to repair plasma membrane lesions. Mutations in dysferlin (dysf) 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 compartment.
