Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins.
Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins.
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DOI：
10.1091/mbc.12.8.2556
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发表时间：
2001-08
影响因子：
3.3
通讯作者：
P. V. Kerkhof;C. Santos;M. Sachse;J. Klumperman;G. Bu;G. Strous
中科院分区：
文献类型：
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作者：
P. V. Kerkhof;C. Santos;M. Sachse;J. Klumperman;G. Bu;G. Strous
泛素-蛋白酶体途径作为选定的膜蛋白的内吞作用的调节器。最近的证据表明，它还可能在膜蛋白的细胞内运输中发挥作用。在这项研究中，几个模型被用来研究泛素-蛋白酶体途径在将内化蛋白分选到溶酶体中的作用。我们发现，在特定蛋白酶体抑制剂的存在下，配体的溶酶体降解被阻止，这些配体仍然与其内吞途径中的受体结合。相反，在内体酸化时从其受体解离的配体在相同的条件下被降解。定量电子显微镜显示，在蛋白酶体抑制剂的存在下，内吞标记牛血清白蛋白-金的摄取或整体分布都没有实质性改变。这些数据表明，泛素-蛋白酶体途径参与了选定的膜蛋白到溶酶体的内切分选步骤，从而提供了一种调节降解的机制。
The ubiquitin-proteasome pathway acts as a regulator of the endocytosis of selected membrane proteins. Recent evidence suggests that it may also function in the intracellular trafficking of membrane proteins. In this study, several models were used to address the role of the ubiquitin-proteasome pathway in sorting of internalized proteins to the lysosome. We found that lysosomal degradation of ligands, which remain bound to their receptors within the endocytic pathway, is blocked in the presence of specific proteasome inhibitors. In contrast, a ligand that dissociates from its receptor upon endosome acidification is degraded under the same conditions. Quantitative electron microscopy showed that neither the uptake nor the overall distribution of the endocytic marker bovine serum albumin-gold is substantially altered in the presence of a proteasome inhibitor. The data suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting step of selected membrane proteins to lysosomes, thereby providing a mechanism for regulated degradation.