LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing

LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
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DOI:
10.1093/emboj/19.21.5720
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发表时间:
2000-11-01
期刊:
影响因子:
11.4
通讯作者:
Yoshimori, T
Yoshimori, T
中科院分区:
生物学1区
文献类型:
--
作者:
Kabeya, Y;Mizushima, N;Yoshimori, T

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哺乳动物细胞自噬体膜的蛋白质组成知之甚少,本文证明了大鼠微管相关蛋白1轻链3(LC 3),一种在酵母中自噬所必需的Apg 8 p的同源物,在加工后与自噬体膜相关联。LC 3的两种形式,称为LC 3-I和LC 3-II,在各种细胞中产生。LC 3-I是胞质的,而LC 3-II是膜结合的。从饥饿大鼠肝脏制备的自噬空泡部分富含LC 3-II,LC 3的免疫电镜显示除了胞质标记之外,自噬体膜的特异性标记,LC 3-II存在于自噬体的内部和外部,突变分析表明,LC 3-I是通过从新合成的LC 3中除去C-末端22个氨基酸,然后将一部分LC 3-I转化为LC 3-II而形成的,LC 3-II的量与自噬体形成的程度相关。LC 3-II是第一个被鉴定的与自噬体膜特异性相关的哺乳动物蛋白。
Little is known about the protein constituents of autophagosome membranes in mammalian cells, Here we demonstrate that the rat microtubule-associated protein 1 light chain 3 (LC3), a homologue of Apg8p essential for autophagy in yeast, is associated to the autophagosome membranes after processing, Two forms of LC3, called LC3-I and -II, were produced post-translationally in various cells. LC3-I is cytosolic, whereas LC3-II is membrane bound, The autophagic vacuole fraction prepared from starved rat liver was enriched with LC3-II, Immunoelectron microscopy on LC3 revealed specific labelling of autophagosome membranes in addition to the cytoplasmic labelling, LC3-II was present both inside and outside of auto-phagosomes, Mutational analyses suggest that LC3-I is formed by the removal of the C-terminal 22 amino acids from newly synthesized LC3, followed by the conversion of a fraction of LC3-I into LC3-II, The amount of LC3-II is correlated with the extent of autophagosome formation. LC3-II is the first mammalian protein identified that specifically associates with autophagosome membranes.