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首页> 外文期刊>Journal of Experimental Botany >Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model
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Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model

机译:可溶性真空蛋白的受体介导的分选:神话,事实和新模型

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Challenging previous dogma, new data indicate that vacuolar sorting receptors recognize their ligands in the endoplasmic reticulum, then release them in the rans-Golgi network before being recycled via clathrin-/retromer-coated vesicles.To prevent their being released to the cell exterior, acid hydrolases are recognized by receptors at some point in the secretory pathway and diverted towards the lytic compartment of the cell (lysosome or vacuole). In animal cells, the receptor is called the mannosyl 6-phosphate receptor (MPR) and it binds hydrolase ligands in the trans-Golgi network (TGN). These ligands are then sequestered into clathrin-coated vesicles (CCVs) because of motifs in the cytosolic tail of the MPR which interact first with monomeric adaptors (Golgi-localized, Gamma-ear-containing, ARF-binding proteins, GGAs) and then with tetrameric (adaptin) adaptor complexes. The CCVs then fuse with an early endosome, whose more acidic lumen causes the ligands to dissociate. The MPRs are then recycled back to the TGN via retromer-coated carriers. Plants have vacuolar sorting receptors (VSRs) which were originally identified in CCVs isolated from pea (Pisum sativum L.) cotyledons. It was therefore assumed that VSRs would have an analogous function in plants to MPRs in animals. Although this dogma has enjoyed wide support over the last 20 years there are many inconsistencies. Recently, results have been published which are quite contrary to it. It now emerges that VSRs and their ligands can interact very early in the secretory pathway, and dissociate in the TGN, which, in contrast to its mammalian counterpart, has a pH of 5.5. Multivesicular endosomes in plants lack proton pump complexes and consequently have an almost neutral internal pH, which discounts them as organelles of pH-dependent receptor-ligand dissociation. These data force a critical re-evaluation of the role of CCVs at the TGN, especially considering that vacuolar cargo ligands have never been identified in them. We propose that one population of TGN-derived CCVs participate in retrograde transport of VSRs from the TGN. We also present a new model to explain how secretory and vacuolar cargo proteins are effectively separated after entering the late Golgi/TGN compartments.
机译:挑战以前的教条,新数据表明,真空分选受体识别其在内质网中的配体,然后在Rans-Golgi网络中释放它们,然后通过克拉肾上腺/回流涂层的囊泡再循环。要防止它们被释放到细胞外部,在分泌途径中的某个点处受体识别酸水解酶,并转向细胞的裂解室(溶酶体或液泡)。在动物细胞中,受体称为甘露糖基6-磷酸受体(MPR),并且它在Trans-golgi网络(TGN)中结合水解酶配体。然后将这些配体隔离成克拉林涂覆的囊泡(CCV),因为MPR的胞质尾部在MPR的细胞骨尾部,其首先用单体适配器(Golgi局部化,含γ-耳,Arf结合蛋白,GGA)而与之相互作用四聚体(Adaptin)适配器配合物。然后用早期内体熔断CCV,其酸性腔更酸性引起配体离解。然后将MPRS通过回涂载流子回收回TGN。植物具有真空分选受体(VSR),其最初鉴定在从豌豆(Pisum Sativum L.)子叶中分离的CCV。因此,假设VSRS将在植物中具有类似的功能对动物的MPRS。虽然这个教条在过去的20年里享受了广泛的支持,但有许多不一致。最近,结果已发表与它相反。它现在出现了VSRS及其配体可以在分泌途径中非常早期互动,并在TGN中解散,与其哺乳动物对应物相比,具有5.5的pH。植物中的多层内体缺乏质子泵复合物,因此具有几乎中性的内部pH值,其折扣为pH依赖性受体 - 配体解离的细胞器。这些数据力强制对TGN在TGN处的作用的关键重新评估,特别是考虑到从未识别过的真空货物配体。我们提出了一种TGN衍生的CCV的人群从TGN参与VSRS的逆行传输。我们还提出了一种新模型来解释在进入晚期Golgi / TGN隔室后如何有效分离分泌物和染色蛋白。

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