「細(xì)胞自噬」作用是個體細(xì)胞遇到生存壓力時,，會自行發(fā)展出包膜企圖吞食或分解入侵的物質(zhì),，以保全其他正常細(xì)胞的自我保護(hù)機(jī)制。近年來科學(xué)家也發(fā)現(xiàn),，細(xì)胞自噬作用與生物發(fā)育以及許多人類疾病,，例如腫瘤、感染與免疫,、心血管疾病,、肌肉病變及神經(jīng)退化性疾病密切相關(guān)。
本院生物化學(xué)研究團(tuán)隊最近成功找出細(xì)胞自噬體形成之分子機(jī)轉(zhuǎn),，發(fā)現(xiàn)一種名為「肌凝蛋白-II」的分子蛋白扮演關(guān)鍵角色,。此新發(fā)現(xiàn)將有助日后治療細(xì)胞自噬失調(diào)相關(guān)疾病的藥物開發(fā)。本研究由生物化學(xué)研究所助研究員陳光超博士及博士生唐弘文主導(dǎo),，其成果已于2011年2月16日發(fā)表于國際重要學(xué)術(shù)期刊 「歐洲分子生物學(xué)研究期刊」(EMBO Journal),。這項研究結(jié)果同時被今年2月份的「自然分子細(xì)胞生物學(xué)評論」( Nature Reviews Molecular Cell Biology 2011,12(2):77)選為重點報導(dǎo)。
研究團(tuán)隊解釋,，細(xì)胞自噬的過程中,，細(xì)胞內(nèi)會產(chǎn)生雙層膜構(gòu)造，將細(xì)胞質(zhì)內(nèi)物質(zhì)包裹起來,，形成細(xì)胞自噬體,，進(jìn)而與溶酶體結(jié)合而分解包裹之物質(zhì)。但是,，細(xì)胞自噬體是如何形成以及自噬體的雙層脂質(zhì)膜來源,，目前科學(xué)界仍未確切知曉。
在本研究中,，陳光超博士研究團(tuán)隊以果蠅和人類細(xì)胞為研究對象,，探討細(xì)胞中「Atg1蛋白質(zhì)激脢」和「細(xì)胞骨架肌動蛋白」調(diào)控細(xì)胞自噬的機(jī)轉(zhuǎn)。他們發(fā)現(xiàn)一個全新的「類肌凝蛋白輕鏈激酶」為「Atg1蛋白質(zhì)激脢」的受質(zhì),，當(dāng)在果蠅或人類細(xì)胞中降低此「類肌凝蛋白輕鏈激酶」或「肌凝蛋白-II」的表現(xiàn)量時,，都會抑制細(xì)胞自噬體的形成,。
另外，他們更進(jìn)一步發(fā)現(xiàn)「Atg1蛋白質(zhì)激脢」對于「肌凝蛋白-II」的活化,，會影響到「Atg9嵌膜蛋白」在高基氏體和細(xì)胞自噬體前驅(qū)構(gòu)造間來回循環(huán)移動,。而「Atg9嵌膜蛋白」被認(rèn)為是自噬體的形成過程中提供脂質(zhì)膜的來源之一。
他們的研究結(jié)果顯示Atg1會經(jīng)由磷酸化此「類肌凝蛋白輕鏈激酶」去調(diào)控「肌凝蛋白-II」的活性及「Atg9嵌膜蛋白」的循環(huán)移動,，以促進(jìn)細(xì)胞自噬體的形成,，而此訊息調(diào)控機(jī)轉(zhuǎn)從果蠅到人類有高度的保留性。這個新發(fā)現(xiàn)的調(diào)控機(jī)制可望為日后治療細(xì)胞自噬失調(diào)相關(guān)疾病帶來新的觀點,。（生物谷Bioon.com）
生物谷推薦原文出處：
The EMBO Journal 30, 636 - 651 (16 February 2011) | doi:10.1038/emboj.2010.338
Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy
Hong-Wen Tang, Yu-Bao Wang, Shiu-Lan Wang, Mei-Hsuan Wu, Shu-Yu Lin and Guang-Chao Chen
Abstract
Autophagy is a membrane-mediated degradation process of macromolecule recycling. Although the formation of double-membrane degradation vesicles (autophagosomes) is known to have a central role in autophagy, the mechanism underlying this process remains elusive. The serine/threonine kinase Atg1 has a key role in the induction of autophagy. In this study, we show that overexpression of Drosophila Atg1 promotes the phosphorylation-dependent activation of the actin-associated motor protein myosin II. A novel myosin light chain kinase (MLCK)-like protein, Spaghetti-squash activator (Sqa), was identified as a link between Atg1 and actomyosin activation. Sqa interacts with Atg1 through its kinase domain and is a substrate of Atg1. Significantly, myosin II inhibition or depletion of Sqa compromised the formation of autophagosomes under starvation conditions. In mammalian cells, we found that the Sqa mammalian homologue zipper-interacting protein kinase (ZIPK) and myosin II had a critical role in the regulation of starvation-induced autophagy and mammalian Atg9 (mAtg9) trafficking when cells were deprived of nutrients. Our findings provide evidence of a link between Atg1 and the control of Atg9-mediated autophagosome formation through the myosin II motor protein.
