A FYVE-finger-containing protein, Rabip4 is a Rab4 effector involved in early endosomal traffic

The small GTPase Rab4 is implicated in endocytosis in all cell types, but a lso plays a specific role in some regulated processes. To better understand the role of Rab4 in regulation of vesicular trafficking, we searched for a n 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 y east two-hybrid system and in the mammalian cell. Rabip4 contains two coile d-coil domains and a FYVE-finger domain. When expressed in CHO cells, Rabip 4 is present in early endosomes, because it is colocated with endogenous Ea rly Endosome Antigen 1, although it is absent from Rab11-positive recycling endosomes and Rab-7 positive late endosomes. The coexpression of Rabip4 wi th active Rab4, but not with inactive Rab4, leads to an enlargement of earl y endosomes, It strongly increases the degree of colocalization of markers of sorting (Rab5) and recycling (Rab11) endosomes with Rab4, Furthermore, t he expression of Rabip4 leads to the intracellular retention of a recycling molecule, the glucose transporter Glut 1, We propose that Rabip4, an effec tor of Rab4, controls early endosomal traffic possibly by activating a back ward transport step from recycling to sorting endosomes.