Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain (Journal article)
Nielsen, E./ Christoforidis, S./ Uttenweiler-Joseph, S./ Miaczynska, M./ Dewitte, F./ Wilm, M./ Hoflack, B./ Zerial, M.
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.
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής|
|Keywords:||Amino Acid Motifs,Amino Acid Sequence,Carrier Proteins/*chemistry/genetics/*metabolism,Cathepsin D/metabolism,Cell Line,Cloning, Molecular,Endosomes/chemistry/*metabolism,Fluorescent Antibody Technique,HeLa Cells,Humans,Lysosomes/chemistry/metabolism,Membrane Fusion,Membrane Microdomains/chemistry/metabolism,Membrane Proteins/chemistry/genetics/*metabolism,Molecular Sequence Data,Munc18 Proteins,Nerve Tissue Proteins/chemistry,Phosphatidylinositol 3-Kinases/metabolism,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/*metabolism|
|Appears in Collections:||Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)|
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