Carroll K S, Hanna J, Simon I, Krise J, Barbero P, Pfeffer S R
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Science. 2001 May 18;292(5520):1373-6. doi: 10.1126/science.1056791.
Mannose 6-phosphate receptors (MPRs) deliver lysosomal hydrolases from the Golgi to endosomes and then return to the Golgi complex. TIP47 recognizes the cytoplasmic domains of MPRs and is required for endosome-to-Golgi transport. Here we show that TIP47 also bound directly to the Rab9 guanosine triphosphatase (GTPase) in its active, GTP-bound conformation. Moreover, Rab9 increased the affinity of TIP47 for its cargo. A functional Rab9 binding site was required for TIP47 stimulation of MPR transport in vivo. Thus, a cytosolic cargo selection device may be selectively recruited onto a specific organelle, and vesicle budding might be coupled to the presence of an active Rab GTPase.
甘露糖6-磷酸受体（MPRs）将溶酶体水解酶从高尔基体转运至内体，然后返回高尔基体复合体。TIP47识别MPRs的胞质结构域，是内体到高尔基体运输所必需的。在此我们表明，TIP47还以其活性的、结合GTP的构象直接结合Rab9鸟苷三磷酸酶（GTP酶）。此外，Rab9增加了TIP47对其货物的亲和力。在体内，TIP47刺激MPR运输需要一个功能性的Rab9结合位点。因此，一种胞质货物选择装置可能被选择性地招募到特定细胞器上，并且囊泡出芽可能与活性Rab GTP酶的存在相关联。
