Wurst is essential for airway clearance and respiratory-tube size control


The Drosophila melanogaster tracheal system and the mammalian lung are branching networks of tubular epithelia that convert during late embryogenesis from liquid- to air-filling1,2,3. Little is known about how respiratory-tube size and physiology are coordinated. Here, we show that the Drosophila wurst gene encodes a unique J-domain transmembrane protein highly conserved in metazoa. In wurst mutants, respiratory-tube length is increased and lumen clearance is abolished, preventing gas filling of the airways. Wurst is essential for clathrin-mediated endocytosis4, which is required for size determination and lumen clearance of the airways. wurst recruits heat shock cognate protein 70-4 and clathrin to the apical membrane of epithelial cells. The sequence conservation of the single Wurst orthologues in mice and humans offer new opportunities for genetic studies of clinically relevant lung syndromes caused by the failure of liquid clearance and respiratory-tube size control.

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Figure 1: Wurst is a conserved protein required for respiratory-tube size control.
Figure 2: Wurst is required for apical ECM organization and respiratory lumen clearance.
Figure 3: Wurst interacts with hsc70-4 and clathrin.
Figure 4: Wurst-dependent endocytosis is essential for tube-size regulation and lumen clearance.

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We thank: C. Samakovlis for communicating unpublished results; M. Affolter, R. Fehon, M. González-Gaitán, L. Liu, B. Moussian, K. Palter, D. F. Ready, U. Schäfer and S. Luschnig for sharing fly stocks and reagents; T. Magin, I. Zinke and B. Fuss for comments on the manuscript; and the members of the Hoch laboratory for helpful discussions. M.B. would like to thank L. Kutschenko, V. Arndt, J. Martini and all members of the Hoch laboratory for technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to M.B. (BE3215) and to M.H. (SFB 645).

Author information

Norther blot, electron microscopic studies and clathrin interaction assay were performed by C. Wingen; molecular analysis of the l(1)G0162 P-element was performed by C. Wolf; all other experiments were performed by M.B.; the wurst project was initiated by M.B. and R.S.; M.H. supervised the research project; M.H. wrote the manuscript; all authors discussed the experimental results.

Correspondence to Michael Hoch.

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Behr, M., Wingen, C., Wolf, C. et al. Wurst is essential for airway clearance and respiratory-tube size control. Nat Cell Biol 9, 847–853 (2007). https://doi.org/10.1038/ncb1611

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