Журнал аллергии и терапии

Абстрактный

Wurst-Mediated Airway Clearance is Required for Postembryonic Development

Anna Lollies, Tamara Krsmanovic, Laura CA Jussen and Matthias Behr*

Tubular organs are required for transport of liquids or gases. The Drosophila tracheal system and the human lungs need to undergo liquid to air transition to enable oxygen transport in the postembryonic or neonatal development respectively. In humans, a failure of airway liquid-clearance can lead to severe clinical syndromes, such as neonatal respiratory distress syndrome or transient tachypnea of newborn. However, the underlying molecular mechanisms are poorly understood. Previously, we identified the transmembrane J-domain protein Wurst as a key regulator of airway clearance in Drosophila. Wurst is involved in endocytosis and recruits clathrin and the associated Heat shock cognate protein 70 to the apical membrane. In wurst mutant embryos airways are oversized and airway liquidclearance is impaired. Here we show that wurst expression in tracheal cells, but not in the respiratory openings, is sufficient to rescue airway clearance and air-filling. We found that only tracheal specific RNAi knock-down of wurst is essential for airway liquid-clearance in post embryonic stages resulting in severe growth arrest and early lethality. In the tracheal wurst knock-down, clathrin accumulated at the apical cell membrane. Cell culture assays identified Wurst co-localization with endocytic markers and co-clustering at the plasma membrane. In summary, our data characterize Wurst as a key regulator of airway liquid-clearance and physiology. Wurst is conserved and a single ortholog was identified in humans, termed DNAJC22. Thus, investigating the molecular function of Wurst/DNAJC22 in airway liquid-clearance will contribute to a better understanding of clinical relevant lung syndromes.