Atg5蛋白调控晚期胞内体和溶酶体的生成

被引：0

作者：

彭俊雅

机构：

[1] 清华大学

关键词：

晚期胞内体/溶酶体再生; Atg5; 自吞噬;

D O I：

暂无

年度学位：

2015

学位类型：

博士

导师：

俞立;

摘要：

细胞自噬是真核细胞一种依赖于溶酶体的降解途径,当细胞遇到各种形式的刺激时,自吞噬将降解细胞自身大分子、细胞器和一些错误折叠的蛋白以帮助细胞缓解应激,自吞噬过程在进化上高度保守。Atg5蛋白在自吞噬过程中起重要的作用,Atg5-Atg12结合系统在自噬体膜的弯曲并招募Atg8(LC3)上起重要作用。我们的研究发现Atg5蛋白同时也在溶酶体和晚期胞内体的形成过程中扮演重要的角色,而这一过程是非自吞噬依赖途径。我们发现,在Atg5基因缺失的细胞中,出现大量的溶酶体和晚期胞内体融合形成的杂交体,这是由于从杂交体抽离晚期胞内体成分的过程受到阻碍,进而晚期胞内体成分的再循环利用过程也被阻断,导致细胞内的杂交体大量滞留,溶酶体和晚期胞内体不能进行再生。我们同时在Atg7,Atg12,Atg9基因(自噬必需基因)缺失细胞中观察晚期胞内体和溶酶体,并不能观察到与Atg5基因缺失的相同现象。晚期胞内体从杂交体抽离这一过程是受环境中的酸碱度调控,而细胞中囊泡内酸性的维持依赖于囊泡上招募的V-ATPase。我们的研究表明,V1-ATPase并不能有效被招募到酸性囊泡上,这直接导致杂交体p H升高,晚期胞内体成分不能从杂交体顺利抽离,进而导致细胞内杂交体的大量滞留。当我们在Atg5基因缺失的细胞中人为降低细胞内的p H值时,受损的溶酶体和晚期胞内体再生过程得到修复,我们看到与WT细胞中类似的晚期胞内体和溶酶体结构。我们的研究阐明了Atg5除自吞噬外的其他作用,也即Atg5在溶酶体和晚期胞内体再生过程中发挥了重要作用。

引用

页数：120

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