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Rab5 regulates motility of early endosomes on microtubules

Nature Cell Biology volume 1, pages 376–382 (1999)Cite this article

Abstract

The small GTPase Rab5 regulates membrane docking and fusion in the early endocytic pathway. Here we reveal a new role for Rab5 in the regulation of endosome interactions with the microtubule network. Using Rab5 fused to green fluorescent protein we show that Rab5-positive endosomes move on microtubules in vivo. In vitro, Rab5 stimulates both association of early endosomes with microtubules and early-endosome motility towards the minus ends of microtubules. Moreover, similarly to endosome membrane docking and fusion, Rab5-dependent endosome movement depends on the phosphatidylinositol-3-OH kinase hVPS34. Thus, Rab5 functionally links regulation of membrane transport, motility and intracellular distribution of early endosomes.

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Figure 1: EGFP–Rab5 co-localizes with early endosomes in A431 cells.
Figure 2: Endosomes positive for EGFP–Rab5 move in a microtubule-dependent fashion in vivo.
Figure 3: Rab5 regulates endosome association with microtubules.
Figure 4: Early endosomes move on microtubules in a Rab5-dependent fashion in vitro.
Figure 5: Rab5 increases the proportion of minus-end-directed endosome movements on microtubules and this effect requires PI(3)K activity.

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Acknowledgements

We thank M. McNiven for MC44 antibodies, B.H. Toh for EEA1 antibodies, and E. Karsenti for tubulin antibodies and purified centrosomes. R. Lippe and M. Miaczynska provided Rab5–RabGDI complex, and H. McBride provided recombinant α-SNAP L294A. E.N. and F.S. are recipients of EMBO Long-term and Max Planck Fellowships, respectively. This work was supported by the Max Planck Gesellschaft, grants from the Human Frontier Science Program (G-432/96), EU TMR (ERB-CT96-0020), and Biomed (BMH4-97-2410) (to M.Z.). J.M.B. is supported by NIH grant GM559692.

Correspondence and requests for materials should be addressed to M.Z.

Supplementary information is available on Nature Cell Biology’s World-Wide Web site at http://cellbio.nature.com.

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  1. Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse, Dresden D-01307, c/o European Molecular Biology Laboratory (EMBL),, Meyerhofstrasse 1,, Heidelberg, 69117, Germany

    Erik Nielsen, Fedor Severin, Anthony A. Hyman & Marino Zerial

  2. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, New York , 10461, USA

    Jonathan M. Backer

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Nielsen, E., Severin, F., Backer, J. et al. Rab5 regulates motility of early endosomes on microtubules. Nat Cell Biol 1, 376–382 (1999). https://doi.org/10.1038/14075

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