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First published online 12 September 2007
doi: 10.1242/jcs.005926

Journal of Cell Science 120, 3457-3464 (2007)
Published by The Company of Biologists 2007
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Research Article

The endocytic control of JAK/STAT signalling in Drosophila

Olivier Devergne, Christian Ghiglione and Stéphane Noselli*

Institute of Developmental Biology and Cancer, CNRS-UMR 6543, University of Nice Sophia-Antipolis, Parc Valrose, 06108 Nice cedex 2, France

* Author for correspondence (e-mail: noselli{at}unice.fr)

Accepted 31 July 2007

Domeless (Dome) is an IL-6-related cytokine receptor that activates a conserved JAK/STAT signalling pathway during Drosophila development. Despite good knowledge of the signal transduction pathway in several models, the role of receptor endocytosis in JAK/STAT activation remains poorly understood. Using both in vivo genetic analysis and cell culture assays, we show that ligand binding of Unpaired 1 (Upd1) induces clathrin-dependent endocytosis of receptor-ligand complexes and their subsequent trafficking through the endosomal compartment towards the lysosome. Surprisingly, blocking trafficking in distinct endosomal compartments using mutants affecting either Clathrin heavy chain, rab5, Hrs or deep orange led to an inhibition of the JAK/STAT pathway, whereas this pathway was unchanged when rab11 was affected. This suggests that internalization and trafficking are both required for JAK/STAT activity. The requirement for clathrin-dependent endocytosis to activate JAK/STAT signalling suggests a model in which the signalling `on' state relies not only on ligand binding to the receptor at the cell surface, but also on the recruitment of the complex into endocytic vesicles on their way to lysozomes. Selective activation of the pool of receptors marked for degradation thus provides a way to tightly control JAK/STAT activity.

Key words: Endocytosis, JAK/STAT, Border cells


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Internal affairs – the STATs

JCS 2007 120: 1904. [Full Text]  



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 DevelopmentHome page
O. Devergne, C. Ghiglione, and S. Noselli
The endocytic control of JAK/STAT signalling in Drosophila
Development, October 15, 2007; 134(20): e1 - e1.
[Full Text]


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