Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome.
Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome.
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DOI：
10.1083/jcb.139.7.1687
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发表时间：
1997-12-29
影响因子：
7.8
通讯作者：
Ohsumi, Y
中科院分区：
文献类型：
--
作者：
Baba, M;Osumi, M;Scott, SV;Klionsky, DJ;Ohsumi, Y
应激条件在细胞水平上引发多种生理反应。自噬是动物、植物和真菌细胞所使用的一个重要过程，它在营养限制条件下允许大分子成分的循环利用，并重塑细胞内结构以促进细胞分化。为了阐明自噬蛋白运输到液泡/溶酶体的分子基础，我们对酵母中的这一途径进行了形态学和生物化学分析。
以液泡水解酶氨肽酶I（API）作为标记物，我们提供的证据表明自噬途径与用于API输入的生物合成途径——细胞质到液泡靶向（Cvt）途径有重叠。在靶向之前，API的前体形式主要作为与球形颗粒的复合物（称为Cvt复合物）定位在细胞质的特定区域。在营养生长期间，Cvt复合物被一个膜囊选择性地包裹，形成一个直径约150纳米的双膜结合结构，然后该结构与液泡膜融合。这个过程在拓扑学上与酵母在饥饿条件下诱导的巨自噬相同（巴巴，M.，武石，K.，巴巴，N.，大隅，Y. 1994.《细胞生物学杂志》124:903 - 913）。然而，与自噬不同的是，API的输入在生长条件下持续进行。这是首次证明利用一种类似自噬的机制来进行液泡水解酶的生物合成运输。另一个重要发现是，当细胞处于饥饿条件下时，Cvt复合物现在被一个更大的自噬体摄取，该自噬体还包含其他细胞质成分；根据环境条件，细胞使用一种替代途径来隔离Cvt复合物并选择性地将API运输到液泡。这些结果共同表明，两个相关但不同的类似自噬的过程参与了液泡驻留蛋白的生物合成以及待降解底物的隔离。
Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of ∼150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903–913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded.
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酵母突变体在细胞质中的分离和表征与液泡蛋白靶向途径的分离。
影响因子：
7.8
作者：
HARDING, TM;MORANO, KA;SCOTT, SV;KLIONSKY, DJ
通讯作者：
KLIONSKY, DJ
影响因子：
7.8
作者：
Scott, SV;Baba, M;Klionsky, DJ
通讯作者：
Klionsky, DJ
影响因子：
4.8
作者：
Chiang, HL;Schekman, R;Hamamoto, S
通讯作者：
Hamamoto, S
影响因子：
64.8
作者：
CHIANG, HL;SCHEKMAN, R
通讯作者：
SCHEKMAN, R
酵母自噬过程的超微结构分析：自噬体的检测及其表征。
影响因子：
7.8
作者：
Baba, M;Takeshige, K;Baba, N;Ohsumi, Y
通讯作者：
Ohsumi, Y