A FYVE-finger-containing protein, Rabip4 is a Rab4 effector involved in early endosomal traffic
A FYVE-finger-containing protein, Rabip4 is a Rab4 effector involved in early endosomal traffic
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DOI：
10.1073/pnas.031586998
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发表时间：
2001-02-13
影响因子：
11.1
通讯作者：
Le Marchand-Brustel, Y
中科院分区：
文献类型：
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作者：
Cormont, M;Mari, M;Le Marchand-Brustel, Y
小 GTP 酶 Rab4 参与所有细胞类型的内吞作用，但也在一些调节过程中发挥特定作用。为了更好地了解 Rab4 在调节囊泡运输中的作用，我们寻找了特异性识别其 GTP 结合形式的效应器。我们克隆了一种普遍存在的 69 kDa 蛋白 Rabip4，它在酵母双杂交系统和哺乳动物细胞中充当 Rab4 效应子。 Rabip4 包含两个卷曲螺旋结构域和一个 FYVE 指结构域。当在 CHO 细胞中表达时，Rabip4 存在于早期内体中，因为它与内源性早期内体抗原 1 位于同一位置，尽管 Rab11 阳性再循环内体和 Rab-7 阳性晚期内体中不存在 Rabip4。 Rabip4 与活性 Rab4 的共表达，但不与无活性的 Rab4 共表达，导致早期内涵体的扩大，它强烈增加了分选标记 (Rab5) 和回收标记 (Rab11) 与 Rab4 的共定位程度，此外，Rabip4 的表达导致回收分子（葡萄糖转运蛋白 Glut 1）在细胞内保留，我们认为 Rabip4（Rab4 的效应子）控制早期内涵体。内体运输可能通过激活从回收到分选内体的后向运输步骤来实现。
The small GTPase Rab4 is implicated in endocytosis in all cell types, but also plays a specific role in some regulated processes. To better understand the role of Rab4 in regulation of vesicular trafficking, we searched for an effector(s) that specifically recognizes its GTP-bound form. We cloned a ubiquitous 69-kDa protein, Rabip4, that behaves as a Rab4 effector in the yeast two-hybrid system and in the mammalian cell. Rabip4 contains two coiled-coil domains and a FYVE-finger domain. When expressed in CHO cells, Rabip4 is present in early endosomes, because it is colocated with endogenous Early Endosome Antigen 1, although it is absent from Rab11-positive recycling endosomes and Rab-7 positive late endosomes. The coexpression of Rabip4 with active Rab4, but not with inactive Rab4, leads to an enlargement of early endosomes, It strongly increases the degree of colocalization of markers of sorting (Rab5) and recycling (Rab11) endosomes with Rab4, Furthermore, the expression of Rabip4 leads to the intracellular retention of a recycling molecule, the glucose transporter Glut 1, We propose that Rabip4, an effector of Rab4, controls early endosomal traffic possibly by activating a backward transport step from recycling to sorting endosomes.