Rab9 GTPase regulates late endosome size and requires effector interaction for its stability
Rab9 GTPase regulates late endosome size and requires effector interaction for its stability
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DOI：
10.1091/mbc.e04-08-0747
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发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Pfeffer, S
中科院分区：
文献类型：
--
作者：
Ganley, IG;Carroll, K;Pfeffer, S
Rab 9 GT3与甘露糖6-磷酸受体（MPR）和47 kDa的尾部相互作用蛋白（TIP 47）一起位于晚期内体微结构域中。为了探索Rab 9对微结构域建立的重要性，我们从培养的细胞中耗尽了蛋白质。Rab 9耗竭降低晚期内体大小，并减少多层和致密小管的晚期内体/溶酶体的数量，但不减少多泡内体。剩余的晚期内体和溶酶体更紧密地聚集在细胞核附近，暗示Rab 9在内体定位中。细胞显示增加的表面MPR和溶酶体相关膜蛋白1。此外，细胞显示出MPR合成增加以及MPR错分选到溶酶体。令人惊讶的是，Rab 9在晚期内体上的稳定性需要与TIP 47相互作用。Rabs被认为是独立的、异戊二烯化的实体，其驻留在膜上或胞质溶胶中，与GDP解离抑制剂结合。这些数据表明Rab 9稳定性受到特异性效应物相互作用的强烈影响。此外，Rab 9及其相互作用的蛋白质似乎对维持特定的晚期内吞隔室和内体/溶酶体定位至关重要。
Rab9 GTPase resides in a late endosome microdomain together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kDa (TIP47). To explore the importance of Rab9 for microdomain establishment, we depleted the protein from cultured cells. Rab9 depletion decreased late endosome size and reduced the numbers of multilamellar and dense-tubule-containing late endosomes/lysosomes, but not multivesicular endosomes. The remaining late endosomes and lysosomes were more tightly clustered near the nucleus, implicating Rab9 in endosome localization. Cells displayed increased surface MPRs and lysosome-associated membrane protein 1. In addition, cells showed increased MPR synthesis in conjunction with MPR missorting to the lysosome. Surprisingly, Rab9 stability on late endosomes required interaction with TIP47. Rabs are thought of as independent, prenylated entities that reside either on membranes or in cytosol, bound to GDP dissociation inhibitor. These data show that Rab9 stability is strongly influenced by a specific effector interaction. Moreover, Rab9 and the proteins with which it interacts seem critical for the maintenance of specific late endocytic compartments and endosome/lysosome localization.