CYTOSKELETAL ELEMENTS ARE REQUIRED FOR THE FORMATION AND MATURATION OF AUTOPHAGIC VACUOLES

被引:169
作者
APLIN, A [1 ]
JASIONOWSKI, T [1 ]
TUTTLE, DL [1 ]
LENK, SE [1 ]
DUNN, WA [1 ]
机构
[1] UNIV FLORIDA,COLL MED,DEPT ANAT & CELL BIOL,GAINESVILLE,FL 32610
关键词
D O I
10.1002/jcp.1041520304
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页码:458 / 466
页数:9
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