Rabenosyn-5, a Novel Rab5 Effector, Is Complexed with Hvps45 and Recruited to Endosomes through a Fyve Finger Domain

Max-Planck-Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
The Journal of Cell Biology (Impact Factor: 9.69). 11/2000; 151(3):601-12.
Source: PubMed

ABSTRACT 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.

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Available from: Bernard Hoflack, Aug 11, 2015
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    • "Interestingly, only the combination of both tethers led to significant fusion , suggesting that one cannot substitute for the other. These two tethers also coordinate Rab function with SNARE assembly on early endosomes, because rabenosyn-5 binds the Sec1/Munc18-like Vps45 protein (Nielsen et al. 2000; Morrison et al. 2008), and EEA1 binds "
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