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A GTPase-activating protein controls Rab5 function in endocytic trafficking

Nature Cell Biology volume 7, pages 887–893 (2005)Cite this article

Abstract

Rab-family GTPases are conserved regulators of membrane trafficking that cycle between inactive GDP-bound and activated GTP-bound states1,2. A key determinant of Rab function is the lifetime of the GTP-bound state3. As Rabs have a low intrinsic rate of GTP hydrolysis, this process is under the control of GTP-hydrolysis-activating proteins (GAPs)1. Due to the large number of Rabs and GAPs that are encoded by the human genome, it has proven difficult to assign specific functional relationships to these proteins. Here, we identify a Rab5-specific GAP (RabGAP-5), and show that RN-Tre (previously described as a Rab5 GAP) acts on Rab41. RabGAP-5 overexpression triggers a loss of the Rab5 effector EEA1 from endosomes and blocks endocytic trafficking. By contrast, depletion of RabGAP-5 results in increased endosome size, more endosome-associated EEA1, and disrupts the trafficking of EGF and LAMP1. RabGAP-5 therefore limits the amount of activated Rab5, and thereby regulates trafficking through endosomes.

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Figure 1: Identification of a specific GAP for Rab5.
Figure 2: RabGAP-5 regulates endocytic trafficking.
Figure 3: RabGAP-5 expression blocks the endocytosis of EGF.
Figure 4: RabGAP-5 is an essential regulator of Rab5.
Figure 5: RabGAP-5 controls endocytic trafficking.

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Acknowledgements

The authors would like to thank R. Neef, U. Grüneberg, M. Clague and S. Urbé for useful discussions during the course of this work. The Max–Planck Society supports research in the group of F.A.B.

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  1. Department of Cell Biology, Max–Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, D-82152, Germany

    Alexander K. Haas, Evelyn Fuchs, Robert Kopajtich & Francis A. Barr

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  1. Alexander K. Haas
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  2. Evelyn Fuchs
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Correspondence to Francis A. Barr.

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Haas, A., Fuchs, E., Kopajtich, R. et al. A GTPase-activating protein controls Rab5 function in endocytic trafficking. Nat Cell Biol 7, 887–893 (2005). https://doi.org/10.1038/ncb1290

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