Sequence-dependent cargo recognition by SNX-BARs mediates retromer-independent transport of CI-MPR.
Sequence-dependent cargo recognition by SNX-BARs mediates retromer-independent transport of CI-MPR.
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DOI：
10.1083/jcb.201703015
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Cullen PJ
中科院分区：
文献类型：
--
作者：
Simonetti B;Danson CM;Heesom KJ;Cullen PJ
通过重新审视retromer在阳离子非依赖性甘露糖6-磷酸受体（CI-MPR）的内体分选中的经典作用，Simonetti等人揭示CI-MPR分选实际上通过SNX 1/2-SNX 5/6膜微管复合物发生，从而重新评估retromer在这一重要转运过程中的作用。跨膜蛋白的内体再循环需要对存在于其细胞内胞质结构域内的基序的序列依赖性识别。在这项研究中，我们重新研究了逆转录聚合物在阳离子非依赖性甘露糖6-磷酸受体（CI-MPR）的序列依赖性内体-高尔基体网络（TGN）转运中的作用。尽管反转录体的敲低或敲除不干扰CI-MPR转运，但反转录体连接的分选连接蛋白（SNX）-Bin、两性霉素和Rvs（BAR）蛋白的靶向导致CI-MPR内体至TGN转运的明显缺陷。逆转录酶连接的SNX-BAR蛋白包含SNX 1或SNX 2与SNX 5或SNX 6的异二聚体组合，并用于调节管状内体分选谱的生物发生。我们确定SNX 5和SNX 6通过识别特定的WLM内体至TGN分选基序与CI-MPR相关。通过验证SNX 1/2-SNX 5/6管状轮廓形成的CI-MPR依赖性，我们提供了将序列依赖性货物识别与内体至TGN运输所需的管状轮廓的生物发生偶联的机制。因此，本研究中提供的数据重新评价了逆转录酶在CI-MPR转运中的作用。
By revisiting the classical role of retromer in endosomal sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR), Simonetti et al. reveal that CI-MPR sorting actually occurs via SNX1/2–SNX5/6 membrane-tubulating complexes, thereby reappraising retromer’s role in this important transport process. Endosomal recycling of transmembrane proteins requires sequence-dependent recognition of motifs present within their intracellular cytosolic domains. In this study, we have reexamined the role of retromer in the sequence-dependent endosome-to–trans-Golgi network (TGN) transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)–Bin, Amphiphysin, and Rvs (BAR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport. The retromer-linked SNX-BAR proteins comprise heterodimeric combinations of SNX1 or SNX2 with SNX5 or SNX6 and serve to regulate the biogenesis of tubular endosomal sorting profiles. We establish that SNX5 and SNX6 associate with the CI-MPR through recognition of a specific WLM endosome-to-TGN sorting motif. From validating the CI-MPR dependency of SNX1/2–SNX5/6 tubular profile formation, we provide a mechanism for coupling sequence-dependent cargo recognition with the biogenesis of tubular profiles required for endosome-to-TGN transport. Therefore, the data presented in this study reappraise retromer’s role in CI-MPR transport.
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影响因子：
5.3
作者：
Fjorback, Anja W.;Seaman, Matthew;Andersen, Olav M.
通讯作者：
Andersen, Olav M.
影响因子：
16.8
作者：
Collins, BM;Skinner, CF;Owen, DJ
通讯作者：
Owen, DJ
影响因子：
3.3
作者：
Horazdovsky, BF;Davies, BA;Emr, SD
通讯作者：
Emr, SD
影响因子：
3.3
作者：
Jia D;Gomez TS;Billadeau DD;Rosen MK
通讯作者：
Rosen MK
DOI：
10.1073/pnas.1410552111
发表时间：
2014-09-02
影响因子：
11.1
作者：
Gallon, Matthew;Clairfeuille, Thomas;Cullen, Peter J.
通讯作者：
Cullen, Peter J.