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 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.
Cormont
M
M
Institut National de la Santé et de la Recherche Médicale (INSERM) E9911, 06107 Nice Cedex 02, France. cormont@unice.fr
Mari
M
M
Galmiche
A
A
Hofman
P
P
Le Marchand-Brustel
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D011992:Endosomes / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D011506:Proteins; C423617:Rufy1 protein, mouse; D020695:rab4 GTP-Binding Proteins