The ESCRT Machinery regulates Retromer dependent Transcytosis of Septate Junction Components in Drosophila

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Abstract

Loss of ESCRT function in Drosophila imaginal discs is known to cause neoplastic overgrowth fuelled by mis-regulation of signalling pathways. Its impact on junctional integrity, however, remains obscure. To dissect the events leading to neoplasia, we used transmission electron microscopy (TEM) on wing imaginal discs temporally depleted of the ESCRT-III core component Shrub. We find a specific requirement for Shrub in maintaining Septate Junction (SJ) integrity by transporting the Claudin Megatrachea (Mega) to the SJ. In absence of Shrub function, Mega is lost from the SJ and becomes trapped on endosomes coated with the endosomal retrieval machinery Retromer. We show that ESCRT function is required for apical localization and mobility of Retromer positive carrier vesicles, which mediate the biosynthetic delivery of Mega to the SJ. Accordingly, loss of Retromer function impairs the anterograde transport of several SJ core components, revealing a novel physiological role for this ancient endosomal agent.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Hendrik Pannen

Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Tim Rapp

Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Thomas Klein

Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

For correspondence
thomas.klein@hhu.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2719-9617

Funding

Deutsche Forschungsgemeinschaft (Sachbeihilfe KL 1028/11-1)

Hendrik Pannen
Tim Rapp
Thomas Klein

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.