The intestine of the nematode Caenorhabditis elegans consists of just 20 enterocyte cells, yet – despite its simplicity – these cells have a similar structure and function to the mammalian intestinal epithelium, with strong apico-basal polarisation and an apical microvillus brush border. Disruption of this polarity and defects in apical membrane trafficking are associated with microvillus inclusion disease (MVID), a severe human genetic disorder. Aurélien Bidaud-Meynard, Gregoire Michaux and colleagues set out to identify new regulators of enterocyte cell polarity in C. elegans through an RNAi screening approach. Through this, they identify a number of components of the V-ATPase complex, which is known to regulate trafficking through endosomal acidification. Intriguingly, although components of both the V0 and V1 subunits are important for apical localisation of polarity proteins, only the V0 sector is required for brush border maintenance. The authors provide evidence that V0 acts upstream of the SNAP29 SNARE and RAB11-mediated exocytosis to ensure the proper formation and maintenance of the apical membrane compartment. Moreover, V0 knockdown recapitulates the cellular phenotypes of MVID, potentially providing a valuable in vivo model to understand the basic mechanisms underlying this disorder.
