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
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/18842
ISSN: 0021-9525
Link: http://www.ncbi.nlm.nih.gov/pubmed/11062261
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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