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Dynein is required for receptor sorting and the morphogenesis of early endosomes

Nature Cell Biology volume 9, pages 113–120 (2007)Cite this article

Abstract

The early endosome is organised into domains to ensure the separation of cargo1,2. Activated mitogenic receptors, such as epidermal growth factor (EGF) receptor, are concentrated into vacuoles enriched for the small GTPase Rab53,4, which progressively exclude nutrient receptors, such as transferrin receptor, into neighbouring tubules4,5,6,7. These vacuoles become enlarged, increase their content of intralumenal vesicles as EGF receptor is sorted from the limiting membrane, and eventually mature to late endosomes8. Maturation is governed by the loss of Rab5 and is accompanied by the movement of endosomes along microtubules towards the cell centre9. Here, we show that EGF relocates to the cell centre in a dynein-dependent fashion, concomitant with the sorting away of transferrin receptor, although it remains in Rab5-positive early endosomes. When dynein function is acutely disrupted, efficient recycling of transferrin from EGF-containing endosomes is retarded, loss of Rab5 is slowed and endosome enlargement is reduced.

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Figure 1: EGF movement is inhibited by acute disruption of dynein.
Figure 2: Motile EGF-containing endosomes are Rab5-positive.
Figure 3: EGF and Tf sort from early endosomes.
Figure 4: CC1 inhibits endosomal sorting of Tf and EGF.
Figure 5: Inhibition of dynein affects endosomal maturation.

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Acknowledgements

We thank our colleagues for their generous gifts of reagents. This work is supported by the Medical Research Council (Grants G9722026, G0001128) and Biotechnology and Biological Sciences Research Council (Grant BB/C512929/1). O.J.D. was supported by a BBSRC research studentship.

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  1. Victoria J. Allan and Philip G. Woodman: These authors contributed equally to this work.

Authors and Affiliations

  1. Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    Owen J. Driskell, Aleksandr Mironov, Victoria J. Allan & Philip G. Woodman

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  2. Aleksandr Mironov
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  3. Victoria J. Allan
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All authors contributed to experimental work and data analysis. O.J.D., V.J.A. and P.G.W. contributed to project planning.

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Correspondence to Victoria J. Allan or Philip G. Woodman.

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The authors declare no competing financial interests.

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Driskell, O., Mironov, A., Allan, V. et al. Dynein is required for receptor sorting and the morphogenesis of early endosomes. Nat Cell Biol 9, 113–120 (2007). https://doi.org/10.1038/ncb1525

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