Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor.
Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor.
复制标题
哺乳动物缩回术在与阳离子非依赖性甘露糖6-磷酸受体分类中的作用。
DOI：
10.1083/jcb.200312055
复制
发表时间：
2004-04
影响因子：
7.8
通讯作者：
Bonifacino, Juan S
中科院分区：
文献类型：
--
作者：
Arighi, Cecilia N;Hartnell, Lisa M;Aguilar, Ruben C;Haft, Carol R;Bonifacino, Juan S
阳离子非依赖性甘露糖6-磷酸受体(CI-MPR)介导溶酶体水解酶前体从TGN到内体的分选。在将水解酶前体释放到内体管腔后，未被占据的受体返回TGN进行进一步的分选。在这里，我们证明了哺乳动物的逆转录复合体参与了这一检索途径。逆转聚体的hVps35亚基与CI-MPR的胞浆结构域相互作用。这种相互作用可能发生在内体隔室，在那里大部分逆转录聚体是定位的。特别是，逆转录聚体与来自早期内体或从早期到晚期内体成熟的中间产物的管状-囊泡型有关。通过RNA干扰耗尽反转录聚合酶可增加CI-MPR的溶酶体周转率，降低细胞内溶酶体水解酶的水平，并导致溶酶体肿胀。这些观察表明，逆转聚体阻止CI-MPR递送到溶酶体，可能是通过隔离到内体衍生的小管，从那里受体返回TGN。
The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway. The hVps35 subunit of retromer interacts with the cytosolic domain of the CI-MPR. This interaction probably occurs in an endosomal compartment, where most of the retromer is localized. In particular, retromer is associated with tubular–vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes. Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes. These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN.