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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

Authors

  • Nielsen E
  • Christoforidis S
  • Uttenweiler-Joseph S
  • Miaczynska M
  • Dewitte F
  • Wilm M
  • Hoflack B
  • Zerial M

Journal

The Journal of cell biology

Publication Data

October 30, 2000

Associated Grants

None

Mesh Terms

  • 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