Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain.
Rab5 regulates endocytic membrane traffic by specifically recruiting cytosolic effector proteins to their site of action on early endosomal membranes. We have characterized a new Rab5 effector complex involved in endosomal fusion events. This complex includes a novel protein, Rabenosyn-5, which, like the previously characterized Rab5 effector early endosome antigen 1 (EEA1), contains an FYVE finger domain and is recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. Rabenosyn-5 is complexed to the Sec1-like protein hVPS45. hVPS45 does not interact directly with Rab5, therefore Rabenosyn-5 serves as a molecular link between hVPS45 and the Rab5 GTPase. This property suggests that Rabenosyn-5 is a closer mammalian functional homologue of yeast Vac1p than EEA1. Furthermore, although both EEA1 and Rabenosyn-5 are required for early endosomal fusion, only overexpression of Rabenosyn-5 inhibits cathepsin D processing, suggesting that the two proteins play distinct roles in endosomal trafficking. We propose that Rab5-dependent formation of membrane domains enriched in phosphatidylinositol-3-phosphate has evolved as a mechanism for the recruitment of multiple effector proteins to mammalian early endosomes, and that these domains are multifunctional, depending on the differing activities of the effector proteins recruited.
Pubmed ID: 11062261 RIS Download
Amino Acid Motifs | Amino Acid Sequence | Carrier Proteins | Cathepsin D | Cell Line | Cloning, Molecular | Endosomes | Fluorescent Antibody Technique | HeLa Cells | Humans | Lysosomes | Membrane Fusion | Membrane Microdomains | Membrane Proteins | Molecular Sequence Data | Munc18 Proteins | Nerve Tissue Proteins | Phosphatidylinositol 3-Kinases | Protein Binding | Protein Processing, Post-Translational | Protein Structure, Tertiary | Protein Transport | Qa-SNARE Proteins | Sequence Alignment | Sequence Homology, Amino Acid | Transfection | Vesicular Transport Proteins | rab5 GTP-Binding Proteins