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Endocytic control of growth factor signalling: multivesicular bodies as signalling organelles

Nature Reviews Molecular Cell Biology volume 13, pages 53–60 (2012)Cite this article

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Abstract

Signal transduction and endocytosis are intertwined processes. The internalization of ligand-activated receptors by endocytosis has classically been thought to attenuate signals by targeting receptors for degradation in lysosomes, but it can also maintain signals in early signalling endosomes. In both cases, localization to multivesicular endosomesen route to lysosomes is thought to terminate signalling. However, during WNT signal transduction, sequestration of the enzyme glycogen synthase kinase 3 (GSK3) inside multivesicular endosomes results in the stabilization of many cytosolic proteins. Thus, the role of endocytosis during signal transduction may be more diverse than anticipated, and multivesicular endosomes may constitute a crucial signalling organelle.

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Figure 1: Current models for the intersection between endocytosis and signalling pathways.
Figure 2: Endocytosis is required for canonical WNT signalling.
Figure 3: Generation of protein half-life biosensors and their potential use in signalling integration studies.
Figure 4: Hypothesis: the dorsal determinants of the Xenopus laevis egg may be endosomal components.

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Acknowledgements

We thank members of our laboratory for comments on the manuscript, the Deutsche Forschungsgemeinschaft for supporting R.D. and the US National Institutes of Health for support. E.M.D.R. is an Investigator of the Howard Hughes Medical Institute.

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  1. Radek Dobrowolski and Edward M. De Robertis are at the Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, California 90095-1662, USA.,

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Dobrowolski, R., De Robertis, E. Endocytic control of growth factor signalling: multivesicular bodies as signalling organelles. Nat Rev Mol Cell Biol 13, 53–60 (2012). https://doi.org/10.1038/nrm3244

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