CYTOSKELETAL ELEMENTS ARE REQUIRED FOR THE FORMATION AND MATURATION OF AUTOPHAGIC VACUOLES
CYTOSKELETAL ELEMENTS ARE REQUIRED FOR THE FORMATION AND MATURATION OF AUTOPHAGIC VACUOLES
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DOI：
10.1002/jcp.1041520304
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发表时间：
1992-09-01
影响因子：
5.6
通讯作者：
DUNN, WA
中科院分区：
文献类型：
--
作者：
APLIN, A;JASIONOWSKI, T;DUNN, WA
我们使用生化和形态学技术评估了细胞骨架元件在自噬降解内源蛋白中的作用。在没有外源氨基酸的情况下，培养的正常大鼠肾细胞中内源蛋白质的降解增强。这种增强的降解状态伴随着自噬泡发生率增加 4 倍。在存在诱导微丝（细胞松弛素 B 和 D）或微管（诺考达唑）解聚的药物的情况下，营养缺乏的细胞中的蛋白质降解并未增强。尽管这些药物对蛋白质降解具有相似的抑制作用，但它们对自噬的影响不同。细胞松弛素 B 和 D 干扰自噬体的形成。在用这些药物处理的细胞中，尽管营养物质耗尽，但自噬泡所代表的分数体积并未显着增加。相反，诺考达唑似乎对自噬体的形成没有影响。相反，这种药物抑制了水解酶的传递，从而导致含有未降解的细胞成分的酸性自噬液泡的积累。
We evaluated the role of cytoskeletal elements in the degradation of endogenous proteins via autophgy using biochemical and morphological techniques. In the absence of exogenous amino acids, degradation of endogenous proteins was enhanced in cultured normal rat kidney cells. This enhanced degradative state was accompanied by a 4-fold increase in the occurrence of autophagic vacuoles. In the presence of drugs that induce the depolymerization of microfilaments (cytochalasins B and D) or microtubules (nocodazole), protein degradation was not enhanced in nutrient-deprived cells. Although these drugs had similar inhibitory effects on the protein degradation, their effect on autophagy differed. Cytochalasins B and D interfered with the formation of the autophagosome. In cells treated with these drugs, the fractional volume represented by autophagic vacuoles was not substantially increased despite nutrient depletion. On the contrary, nocodazole appeared to have no effect on the formation of autophagosomes. Instead, this drug suppressed the delivery of hydrolytic enzymes, thereby resulting in an accumulation of acidic autophagic vacuoles containing undegraded cellular components.