Rabenosyn-5, a Novel Rab5 Effector, Is Complexed with Hvps45 and Recruited to Endosomes through a Fyve Finger Domain
| Autor: | Marino Zerial, Bernard Hoflack, Marta Miaczynska, Sandrine Uttenweiler-Joseph, Erik Nielsen, Frédérique Dewitte, Savvas Christoforidis, Matthias Wilm |
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| Přispěvatelé: | Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, European Molecular Biology Laboratory [Heidelberg] (EMBL), Institut de biologie de Lille - UMS 3702 (IBL), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), E. Nielsen, S. Christofordis, and M. Miaczynska were recipients of European Molecular Biology Organization (EMBO) Long-term, Max-Planck, and Human Frontier Science Program Fellowships, respectively. This work was supported by the Max Planck Gesellschaft and by grants from the Human Frontier Science Program (RG-432/96), European Union-Training and Mobility of Researchers (EU TMR) (ERB-CT96-0020), and Biomed (BMH4-97-2410) (M. Zerial)., We are grateful to Drs. A. Klip, R. Piper, H. Stenmark, and R. Scheller for providing antibodies and plasmids. We would also like to thank A. Giner for technical assistance. Special thanks to Dr. H. McBride and S. De Renzis for valuable discussions and critical reading of the manuscript., Danish Road Institute, University of Ioannina, Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Cell Biology Programme, European Molecular Biology Laboratory, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Munc18 Proteins
MESH: Sequence Homology Amino Acid Endocytic cycle Vesicular Transport Proteins Fluorescent Antibody Technique MESH: Amino Acid Sequence Nerve Tissue Proteins/chemistry Membrane Fusion MESH: Amino Acid Motifs MESH: Protein Structure Tertiary 0302 clinical medicine MESH: Qa-SNARE Proteins MESH: Fluorescent Antibody Technique ComputingMilieux_MISCELLANEOUS 0303 health sciences Effector Cell biology MESH: Endosomes/chemistry Membrane Microdomains/chemistry/metabolism Phosphatidylinositol 3-Kinases/metabolism MESH: Protein Transport rab5 GTP-Binding Proteins/*metabolism MESH: Membrane Proteins/chemistry Molecular Sequence Data MESH: Sequence Alignment MESH: Carrier Proteins/chemistry Endosomes Transfection MESH: Membrane Fusion EEA1 03 medical and health sciences MESH: Carrier Proteins/genetics Humans MESH: Protein Binding MESH: Cloning Molecular Amino Acid Sequence MESH: Humans MESH: Molecular Sequence Data Cathepsin D/metabolism Rabenosyn-5 Protein Structure Tertiary MESH: Cell Line FYVE domain MESH: Phosphatidylinositol 3-Kinases/metabolism Carrier Proteins 030217 neurology & neurosurgery HeLa Cells MESH: Cathepsin D/metabolism [SDV]Life Sciences [q-bio] Amino Acid Motifs Lysosomes/chemistry/metabolism hVPS45 Cathepsin D Phosphatidylinositol 3-Kinases Rab5 Carrier Proteins/*chemistry/genetics/*metabolism Cloning Molecular Qa-SNARE Proteins RING finger domain MESH: rab5 GTP-Binding Proteins/metabolism Protein Transport MESH: Nerve Tissue Proteins/chemistry Original Article MESH: Lysosomes/chemistry Membrane Proteins/chemistry/genetics/*metabolism Protein Binding Endosome MESH: Membrane Microdomains/chemistry Nerve Tissue Proteins Biology Cell Line MESH: Membrane Proteins/genetics Membrane Microdomains MESH: Carrier Proteins/metabolism endocytosis MESH: Membrane Proteins/metabolism [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology 030304 developmental biology rab5 GTP-Binding Proteins MESH: Vesicular Transport Proteins Sequence Homology Amino Acid MESH: Transfection Membrane Proteins MESH: Endosomes/metabolism Cell Biology MESH: Membrane Microdomains/metabolism MESH: Lysosomes/metabolism Membrane protein MESH: Munc18 Proteins MESH: Protein Processing Post-Translational MESH: HeLa Cells Lysosomes Protein Processing Post-Translational Sequence Alignment Endosomes/chemistry/*metabolism |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2000, 151 (3), pp.601-612. ⟨10.1083/jcb.151.3.601⟩ The Journal of Cell Biology Journal of Cell Biology, 2000, 151 (3), pp.601-612. ⟨10.1083/jcb.151.3.601⟩ |
| ISSN: | 0021-9525 1540-8140 |
| DOI: | 10.1083/jcb.151.3.601⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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